Is ITGA2 p.Pro546= (c.1638C>T) pathogenic?

ITGA2 p.Pro546= (c.1638C>T) is classified Benign/Likely benign in ITGA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-15). Ultra-rare (popmax 0.0209%, nfe); Associated with platelet-type bleeding disorder 9.

What condition is associated with ITGA2 p.Pro546= (c.1638C>T)?

ITGA2 p.Pro546= (c.1638C>T) is associated with platelet-type bleeding disorder 9 (ClinVar).

How common is ITGA2 p.Pro546= (c.1638C>T) in the general population?

ITGA2 p.Pro546= (c.1638C>T) is ultra-rare (popmax 0.0209%, nfe) (gnomAD).

ITGA2 p.Pro546=

c.1638C>T · rs199602142 · VCV353756

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, nfe)

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 -15	GERP -5
Overall
CADD	1.743	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0209% European (non-Finnish) · 247/1,179,150 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.018%

Overall 0.0253% 408/1,612,724 alleles · ultra-rare exomes 358/1,460,734 · genomes 50/151,990 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.222%	451
European (non-Finnish)grpmax	0.0209%	4,774
Remaining individualsnot grpmax-eligible	0.0208%	4,802
African / African-American	0.00534%	18,724
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,542
Admixed American	0.00167%	59,848

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro546=
Coding: c.1638C>T
MANE Select: NM_002203
dbSNP: rs199602142
Type: single nucleotide variant
Location: chr5:53064947 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.80 · 23 PDB

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-pro546 (accessed [today's date]).

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