# NM_152906.7(TANGO2):c.828C>T (p.Ser276=)

https://sugi.bio/variant/tango2-p-ser276

## Summary

**TANGO2 p.Ser276= (c.828C>T)** is classified **Likely benign** in TANGO2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). Very rare (popmax 0.00133%, afr).

**At a glance:** Likely benign · review: Single submitter · rsID rs2147866464 · 1 submitter · very rare (popmax 0.00133%, afr)

## For patients & families {#patients}

This is a change in the TANGO2 gene that is classified as likely benign — not considered disease-causing, submitted by 1 submitter.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

**Support & next steps:** [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [TANGO2](https://sugi.bio/atlas/gene/TANGO2/) |
| Protein change (HGVS p.) | p.Ser276= |
| Coding change (HGVS c.) | c.828C>T |
| MANE Select transcript | [NM_152906](https://www.ncbi.nlm.nih.gov/nuccore/NM_152906) |
| dbSNP | [rs2147866464](https://www.ncbi.nlm.nih.gov/snp/rs2147866464/) |
| Variant type | single nucleotide variant |
| Location | chr22:20064659-20064659 (GRCh38) |
| ClinVar | [VCV1564438](https://www.ncbi.nlm.nih.gov/clinvar/variation/1564438/) |

**All HGVS expressions:** `NC_000022.10:g.20052182C>T`, `NC_000022.11:g.20064659C>T`, `NG_046857.1:g.52660C>T`, `NM_001283106.3:c.828C>T`, `NM_001283116.3:c.828C>T`, `NM_001283129.3:c.951C>T`, `NM_001283148.3:c.*67C>T`, `NM_001283154.3:c.*67C>T`, `NM_001283179.3:c.642C>T`, `NM_001283186.3:c.642C>T`, `NM_001283199.3:c.603C>T`, `NM_001283215.3:c.*95C>T`, `NM_001283235.3:c.534C>T`, `NM_001283248.3:c.*164C>T`, `NM_001322141.2:c.1107C>T`, `NM_001322142.2:c.984C>T`, `NM_001322143.2:c.951C>T`, `NM_001322144.2:c.*67C>T`, `NM_001322145.2:c.765C>T`, `NM_001322146.2:c.882C>T`, `NM_001322147.2:c.765C>T`, `NM_001322148.2:c.726C>T`, `NM_001322149.2:c.726C>T`, `NM_001322150.2:c.690C>T`, `NM_001322153.2:c.690C>T`, `NM_001322155.2:c.690C>T`, `NM_001322160.2:c.*67C>T`, `NM_001322163.2:c.642C>T`, `NM_001322166.2:c.642C>T`, `NM_001322167.2:c.642C>T`, `NM_001322169.2:c.*67C>T`, `NM_001322171.2:c.534C>T`, `NM_001322172.2:c.534C>T`, `NM_001322173.2:c.534C>T`, `NM_001322174.2:c.534C>T`, `NM_001322175.2:c.534C>T`, `NM_152906.7:c.828C>T`, `NR_104274.3:n.623C>T`, `NR_104275.3:n.863C>T`, `NR_136206.2:n.841C>T`, `NR_136211.2:n.1027C>T`, `NR_136212.1:n.925C>T`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP 0.335, GERP 0.173, phastCons 0.992 — weakly conserved position
- CADD: **PHRED 11.7**. No single ClinGen-calibrated threshold exists and the expert panels that use CADD disagree — GUCY2D/AIPL1 require ≥ 20.0 for an untranslated-region variant, ABCA4 ≥ 28.1 for a synonymous or indel variant, the Pulmonary Hypertension panel imports Pejaver 2022's missense-calibrated numbers, and the Antibody Deficiencies panel declines CADD entirely for PIK3CD. CADD v1.7 also incorporates Zoonomia phyloP, so it partly re-expresses the conservation above. *Descriptive; no threshold applied.*
- SpliceAI: **below the reporting threshold**. This position is scored for a different substitution (C>G, Δ1.00 donor gain), so this allele was evaluated and its deltas all fell under Δ0.2 — a prediction of no splicing effect for this allele, not a gap in our data. *No ACMG code assigned.*
- Population frequency (gnomAD v4.1): grpmax **0.00133%** (afr) · 1/75,074 in the highest group · 1/1,614,076 alleles overall — very rare (popmax 0.00133%, afr).

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**TANGO2** population constraint: LOEUF 0.914, pLI 8.371e-05, missense-Z 0.59913. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **276** lies in a UniProt-annotated variant site (in mecrcn); a UniProt-annotated variant site (in mecrcn; uncertain significance).

AlphaFold model confidence (whole protein): pLDDT 95.43, 90% of residues very-high.

**3 experimental structure(s)** (PDB): [8SV7](https://www.rcsb.org/structure/8SV7), [9BWA](https://www.rcsb.org/structure/9BWA), [9N1S](https://www.rcsb.org/structure/9N1S).

## Clinical significance {#significance}

**Likely benign** — review status Single submitter *(criteria provided, single submitter)*, last evaluated 2021-08-09.

**Submitter consensus:** unanimous (1/1 Likely benign).

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Likely benign | criteria provided, single submitter | clinical testing | 2021-08-09 |

**Reported phenotype names (ClinVar):** not provided, none provided.

## Similar variants {#similar}

Related TANGO2 variant pages (same residue, condition, or type): [TANGO2 c.451+2T>A](/variant/tango2-c-451-plus-2t-a), [TANGO2 c.57-1G>C](/variant/tango2-c-57-minus-1g-c), [TANGO2 c.605+1G>A](/variant/tango2-c-605-plus-1g-a), [TANGO2 c.711-3C>G](/variant/tango2-c-711-minus-3c-g), [TANGO2 p.Arg140Ter](/variant/tango2-p-arg140ter), [TANGO2 p.Arg32Ter](/variant/tango2-p-arg32ter), [TANGO2 p.Arg86Ter](/variant/tango2-p-arg86ter), [TANGO2 p.Arg88Ter](/variant/tango2-p-arg88ter).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); gnomAD v4.1 (Broad Institute, built 2026-10-15); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-10-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 1564438). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*