Is ITGA2 p.Ala331= (c.993A>G) pathogenic?

ITGA2 p.Ala331= (c.993A>G) is classified Benign/Likely benign in ITGA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-26). Common (popmax 16.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with platelet-type bleeding disorder 9.

What condition is associated with ITGA2 p.Ala331= (c.993A>G)?

ITGA2 p.Ala331= (c.993A>G) is associated with platelet-type bleeding disorder 9 (ClinVar).

ITGA2 p.Ala331=

Q: How common is ITGA2 p.Ala331= (c.993A>G) in the general population?

ITGA2 p.Ala331= (c.993A>G) is common (popmax 16.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.993A>G · rs3212523 · VCV353747

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 16.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

platelet-type bleeding disorder 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP -5.2, phastCons 0.28
Overall
CADD	6.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.8% African / African-American · 12,527/74,762 alleles

Filtering AF 16.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 16.4%

Overall 8.94% 143,860/1,609,684 alleles · common exomes 127,845/1,457,578 · genomes 16,015/152,106 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.8%	6
Middle Eastern	15.1%	7
Ashkenazi Jewishnot grpmax-eligible	11.4%	9
South Asian	9.71%	10
Remaining individualsnot grpmax-eligible	9.56%	10
European (non-Finnish)	8.8%	11
Admixed American	6.39%	16
Finnishnot grpmax-eligible	5.32%	19
Amishnot grpmax-eligible	3.84%	26
East Asian	3.31%	30

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: ITGA2
Protein: p.Ala331=
Coding: c.993A>G
MANE Select: NM_002203
dbSNP: rs3212523
Type: single nucleotide variant
Location: chr5:53056046 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 23 PDB
Residue 331: the vwfa domain; an α-helix

Full ITGA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

platelet-type bleeding disorder 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITGA2 p.Asn57Lys Uncertain significance ★★ ⚠ same condition
ITGA2 p.Gln690Arg Uncertain significance ★★ ⚠ same condition
ITGA2 p.Gly201Asp Uncertain significance ★★ ⚠ same condition
ITGA2 p.Gly205Val Uncertain significance ★★ ⚠ same condition
ITGA2 c.1312+12T>C Benign/Likely benign ★★ same condition
ITGA2 c.1807-6T>C Benign/Likely benign ★★ same condition
ITGA2 c.2236-62T>C Benign ★★ same condition
ITGA2 c.2742-4A>G Benign/Likely benign ★★ 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/itga2-p-ala331 (accessed [today's date]).

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