Is ITGA2 p.Phe253= (c.759C>T) pathogenic?

ITGA2 p.Phe253= (c.759C>T) is classified Benign/Likely benign in ITGA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-11-26). Common (popmax 44.6%, amr) — too common for a highly-penetrant pathogenic allele; Associated with platelet-type bleeding disorder 9.

What condition is associated with ITGA2 p.Phe253= (c.759C>T)?

ITGA2 p.Phe253= (c.759C>T) is associated with platelet-type bleeding disorder 9 (ClinVar).

ITGA2 p.Phe253=

Q: How common is ITGA2 p.Phe253= (c.759C>T) in the general population?

ITGA2 p.Phe253= (c.759C>T) is common (popmax 44.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.759C>T · rs1126643 · VCV353741

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 44.6%, amr) — 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 0.15	GERP -1.1, phastCons 0.93
Overall
CADD	7.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 44.6% Admixed American · 26,752/59,936 alleles

Filtering AF 44.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 44%

Overall 39.1% 630,746/1,611,596 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	44.6%	2
Amishnot grpmax-eligible	42.2%	2
European (non-Finnish)	39.9%	3
Finnishnot grpmax-eligible	39.6%	3
Remaining individualsnot grpmax-eligible	38.7%	3
Ashkenazi Jewishnot grpmax-eligible	37.8%	3
Middle Eastern	37.1%	3
South Asian	36.4%	3
East Asian	35.2%	3
African / African-American	28.9%	3

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.Phe253=
Coding: c.759C>T
MANE Select: NM_002203
dbSNP: rs1126643
Type: single nucleotide variant
Location: chr5:53051539 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 23 PDB
Residue 253: an α-helix; the vwfa domain

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-phe253 (accessed [today's date]).

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