Is GP1BA p.Ala172Val (c.515C>T) pathogenic?

GP1BA p.Ala172Val (c.515C>T) is classified Pathogenic in GP1BA (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-16). AlphaMissense: likely pathogenic (0.7713); Very rare (popmax 0.00017%, nfe); Associated with GP1BA-related disorders.

What condition is associated with GP1BA p.Ala172Val (c.515C>T)?

GP1BA p.Ala172Val (c.515C>T) is associated with GP1BA-related disorders, Bernard-Soulier syndrome, type A2, autosomal dominant, platelet-type von Willebrand disease (ClinVar).

How common is GP1BA p.Ala172Val (c.515C>T) in the general population?

GP1BA p.Ala172Val (c.515C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about GP1BA p.Ala172Val (c.515C>T)?

AlphaMissense predicts likely pathogenic (score 0.7713) — an in-silico prediction, not a clinical call.

GP1BA p.Ala172Val

c.515C>T · rs121908065 · VCV4156

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.7713 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

GP1BA-related disorders

Computational evidence

Protein change
AlphaMissense	0.7713	likely pathogenic ✓ concordant with ClinVar · top 8% in GP1BA
REVEL	0.359	indeterminate
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 1,223 bp · p 0.011 · regional, not allelic
Overall
CADD	21.4	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 0.00017% European (non-Finnish) · 2/1,179,762 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,866 alleles · very rare exomes 2/1,461,550 · genomes 0/152,316 · 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: GP1BA
Protein: p.Ala172Val
Coding: c.515C>T
MANE Select: NM_000173
dbSNP: rs121908065
Type: single nucleotide variant
Location: chr17:4933119 (GRCh38)
Gene constraint: LOEUF 1.289 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 64.65 · 22 PDB
Residue 172: a UniProt-annotated variant site (in bss and bssa2)

Full GP1BA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

GP1BA-related disorders

Also linked: Bernard-Soulier syndrome, type A2, autosomal dominant platelet-type von Willebrand disease Bernard-Soulier syndrome nonarteritic anterior ischemic optic neuropathy, susceptibility to

Similar variants

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GP1BA p.Glu347Ter Likely pathogenic ★★★ same condition
GP1BA p.Leu145Pro Likely pathogenic ★★★ same condition
GP1BA p.Ser267Ter Likely pathogenic ★★★ same condition
GP1BA p.Ser486Ter Likely pathogenic ★★★ same condition
GP1BA p.Trp223Gly Likely pathogenic ★★★ 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/gp1ba-p-ala172val (accessed [today's date]).

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