# NM_002231.4(CD82):c.699C>T (p.Gly233=)

https://sugi.bio/variant/cd82-p-gly233

## Summary

**CD82 p.Gly233= (c.699C>T)** is classified **Benign** in CD82 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2017-10-19). Low-frequency (popmax 3.97%, afr).

**At a glance:** Benign · review: Multiple submitters · rsID rs79095986 · 3 submitters · low-frequency (popmax 3.97%, afr)

## For patients & families {#patients}

This is a change in the CD82 gene that is classified as benign — not considered disease-causing, submitted by 3 submitters.

*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 | [CD82](https://sugi.bio/atlas/gene/CD82/) |
| Protein change (HGVS p.) | p.Gly233= |
| Coding change (HGVS c.) | c.699C>T |
| MANE Select transcript | [NM_002231](https://www.ncbi.nlm.nih.gov/nuccore/NM_002231) |
| dbSNP | [rs79095986](https://www.ncbi.nlm.nih.gov/snp/rs79095986/) |
| Variant type | single nucleotide variant |
| Location | chr11:44618696-44618696 (GRCh38) |
| ClinVar | [VCV786594](https://www.ncbi.nlm.nih.gov/clinvar/variation/786594/) |

**All HGVS expressions:** `NC_000011.10:g.44618696C>T`, `NC_000011.9:g.44640246C>T`, `NG_023234.1:g.58106C>T`, `NM_001024844.2:c.624C>T`, `NM_002231.4:c.699C>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 0.069, GERP 0.164, phastCons 0.89 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- CADD: **PHRED 9.745**. 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, Δ0.34 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 **3.97%** (afr) · FAF95 3.85% · FAF99 3.81% · 2,979/74,982 in the highest group · 3,545/1,613,228 alleles overall — low-frequency (popmax 3.97%, afr).

| Ancestry group | Allele frequency | 1 in |
| --- | --- | --- |
| African / African-American (grpmax) | 3.97% | 25 |
| Admixed American | 0.378% | 264 |
| Remaining individuals (not grpmax-eligible) | 0.283% | 353 |
| Middle Eastern | 0.182% | 551 |
| East Asian | 0.0335% | 2,987 |
| South Asian | 0.0187% | 5,357 |
| European (non-Finnish) | 0.01% | 9,998 |
| Ashkenazi Jewish (not grpmax-eligible) | 0.00338% | 29,600 |

*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}

**CD82** population constraint: LOEUF 1.221, pLI 1.2573e-09, missense-Z 0.14577. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}


AlphaFold model confidence (whole protein): pLDDT 88.31, 65% of residues very-high.

**1 experimental structure(s)** (PDB): [9HT6](https://www.rcsb.org/structure/9HT6).

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2017-10-19.

**Submitter consensus:** unanimous (2/2 Benign).

**Submission history:** 18 submissions (2017); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2017-10-19 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |
| Dr. Peter K. Rogan Lab, Western University |  | no classification provided | in vitro |  |

**Reported phenotype names (ClinVar):** not provided, Sarcoma, Acute myeloid leukemia, Nonpapillary renal cell carcinoma, Lung cancer, Clear cell carcinoma of kidney, Uterine corpus endometrial carcinoma, Cervical cancer, none provided.

## Similar variants {#similar}

Related CD82 variant pages (same residue, condition, or type): [CD82 p.Leu248=](/variant/cd82-p-leu248), [CD82 p.Val62=](/variant/cd82-p-val62), [CD82 p.Ala195Val](/variant/cd82-p-ala195val), [CD82 p.Arg254Trp](/variant/cd82-p-arg254trp), [CD82 p.Arg53Ser](/variant/cd82-p-arg53ser), [CD82 p.Asn109Ser](/variant/cd82-p-asn109ser), [CD82 p.Asn17Ser](/variant/cd82-p-asn17ser), [CD82 p.Asn227Thr](/variant/cd82-p-asn227thr).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); 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 2026-07-14); 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 786594). 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.*