Is GP6 p.Val232Ile (c.694G>A) pathogenic?

GP6 p.Val232Ile (c.694G>A) is classified Likely benign in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.0713); Very rare (popmax 0.00179%, nfe); Associated with Inborn genetic diseases.

What condition is associated with GP6 p.Val232Ile (c.694G>A)?

GP6 p.Val232Ile (c.694G>A) is associated with Inborn genetic diseases (ClinVar).

How common is GP6 p.Val232Ile (c.694G>A) in the general population?

GP6 p.Val232Ile (c.694G>A) is very rare (popmax 0.00179%, nfe) (gnomAD).

What do computational predictors say about GP6 p.Val232Ile (c.694G>A)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

GP6 p.Val232Ile

c.694G>A · rs951449463 · VCV2232951

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00179%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -7.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.3	GERP -1.9
Overall
CADD	0.338	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00179% European (non-Finnish) · 21/1,175,180 alleles

Filtering AF 0.00115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000975%

Overall 0.00137% 22/1,608,896 alleles · very rare exomes 22/1,456,560 · genomes 0/152,336 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00179%	55,961
Admixed American	0.00167%	60,026

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: GP6
Protein: p.Val232Ile
Coding: c.694G>A
MANE Select: NM_016363
dbSNP: rs951449463
Type: single nucleotide variant
Location: chr19:55018682 (GRCh38)
Gene constraint: LOEUF 1.734 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 76.52 · 6 PDB

Full GP6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GP6 c.*106A>C Uncertain significance ★★ same condition
GP6 c.*189C>T Uncertain significance ★★ same condition
GP6 c.*304C>T Uncertain significance ★★ same condition
GP6 c.*523G>C Uncertain significance ★★ same condition
GP6 c.*531T>C Uncertain significance ★★ same condition
GP6 p.Arg262Cys Uncertain significance ★★ ⚠ same condition
GP6 p.Arg299Trp Uncertain significance ★★ ⚠ same condition
GP6 p.Arg319Trp Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/gp6-p-val232ile (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown