Is GP6 p.Val271Ala (c.812T>C) pathogenic?

GP6 p.Val271Ala (c.812T>C) is classified Uncertain significance in GP6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.1465); Very rare (popmax 0.00231%, eas).

How common is GP6 p.Val271Ala (c.812T>C) in the general population?

GP6 p.Val271Ala (c.812T>C) is very rare (popmax 0.00231%, eas) (gnomAD).

What do computational predictors say about GP6 p.Val271Ala (c.812T>C)?

AlphaMissense predicts likely benign (score 0.1465) — an in-silico prediction, not a clinical call.

GP6 p.Val271Ala

c.812T>C · VCV3365747

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1465 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00231%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1465	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.15, phastCons 0.15
Overall
CADD	4.549	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00231% East Asian · 1/43,208 alleles

Overall 6.34e-05% 1/1,577,336 alleles · very rare exomes 1/1,425,062 · genomes 0/152,274 · joint denominator

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.Val271Ala
Coding: c.812T>C
MANE Select: NM_016363
Type: single nucleotide variant
Location: chr19:55015129 (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

Similar variants

GP6 p.Trp160Ter Pathogenic ★★ same type
GP6 c.*106A>C Uncertain significance ★★ same type
GP6 c.*189C>T Uncertain significance ★★ same type
GP6 c.*304C>T Uncertain significance ★★ same type
GP6 c.*523G>C Uncertain significance ★★ same type
GP6 c.*531T>C Uncertain significance ★★ same type
GP6 c.*820T>C Uncertain significance ★★ same type
GP6 p.Arg262Cys Uncertain significance ★★ ⚠ same type

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-val271ala (accessed [today's date]).

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