# NM_020469.4(ABO):c.188G= (p.Arg63=)

https://sugi.bio/variant/abo-p-arg63

## Summary

**ABO p.Arg63= (c.188G=)** is classified **Benign** in ABO (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-19). Absent from gnomAD v4.1.

**At a glance:** Benign · review: Multiple submitters · 2 submitters · absent from gnomAD v4.1

## For patients & families {#patients}

This is a change in the ABO gene that is classified as benign — not considered disease-causing, submitted by 2 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 | [ABO](https://sugi.bio/atlas/gene/ABO/) |
| Protein change (HGVS p.) | p.Arg63= |
| Coding change (HGVS c.) | c.188G= |
| Variant type | Variation |
| Location | chr9:133259834-133259834 (GRCh38) |
| ClinVar | [VCV768332](https://www.ncbi.nlm.nih.gov/clinvar/variation/768332/) |

**All HGVS expressions:** `LRG_792:g.20381=`, `LRG_792t1:c.188=`, `NC_000009.11:g.136135238T>C`, `NC_000009.12:g.133259834=`, `NG_006669.2:g.20381=`, `NM_020469.4:c.188G=`

## 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 -1.876, GERP -3.22 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- SpliceAI: **not assessed** — no allele at this position is in our SpliceAI release, either because it lies outside the scored MANE transcript scope or because every allele is below Δ0.2. We cannot tell which, so this claims neither; absence is not evidence against a splicing effect.
- Population frequency: **absent from gnomAD v4.1** — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

*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}

**ABO** population constraint: LOEUF 1.416, pLI 2.3242e-06, missense-Z 0.14459. *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 **63** lies in a UniProt-annotated variant site (in).

AlphaFold model confidence (whole protein): pLDDT 89.59, 82% of residues very-high.

**151 experimental structure(s)** (PDB): [1LZ0](https://www.rcsb.org/structure/1LZ0), [1LZ7](https://www.rcsb.org/structure/1LZ7), [1LZI](https://www.rcsb.org/structure/1LZI), [1LZJ](https://www.rcsb.org/structure/1LZJ), [1R7T](https://www.rcsb.org/structure/1R7T), [1R7U](https://www.rcsb.org/structure/1R7U) — incl. mutant structure 1WSZ.

## What this gene does {#gene-function}

*Describes the biological roles of ABO (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** ABO's established molecular role includes nucleotide binding.


### Pathways affected {#pathways}

ABO participates in **1 Reactome pathway** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| [ABO blood group biosynthesis](https://reactome.org/content/detail/R-HSA-9033807) | curated |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** nucleotide binding, antigen binding, manganese ion binding.

## Clinical significance {#significance}

**Benign** — review status Multiple submitters *(criteria provided, multiple submitters, no conflicts)*, last evaluated 2019-12-19.

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

**Submission history:** 2 submissions (2019); classifications have been stable.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| Labcorp Genetics (formerly Invitae), Labcorp | Benign | criteria provided, single submitter | clinical testing | 2019-12-19 |
| Breakthrough Genomics, Breakthrough Genomics | Benign | criteria provided, single submitter | not provided |  |

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

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-14); 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 768332). 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.*