Is ITGA2B p.Phe1024Ile (c.3070T>A) pathogenic?

ITGA2B p.Phe1024Ile (c.3070T>A) is classified Conflicting classifications of pathogenicity in ITGA2B (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-03-05). AlphaMissense: likely pathogenic (0.926); Absent from gnomAD v4.1; Associated with platelet-type bleeding disorder 16.

What condition is associated with ITGA2B p.Phe1024Ile (c.3070T>A)?

ITGA2B p.Phe1024Ile (c.3070T>A) is associated with platelet-type bleeding disorder 16 (ClinVar).

How common is ITGA2B p.Phe1024Ile (c.3070T>A) in the general population?

ITGA2B p.Phe1024Ile (c.3070T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ITGA2B p.Phe1024Ile (c.3070T>A)?

AlphaMissense predicts likely pathogenic (score 0.926) — an in-silico prediction, not a clinical call.

ITGA2B p.Phe1024Ile

c.3070T>A · rs1331554337 · VCV2572659

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.926 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

platelet-type bleeding disorder 16

Computational evidence

Protein change
AlphaMissense	0.926	likely pathogenic · top 6% in ITGA2B
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -11.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 13 kb · p 0.0004 · regional, not allelic
Overall
CADD	25.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITGA2B
Protein: p.Phe1024Ile
Coding: c.3070T>A
MANE Select: NM_000419
dbSNP: rs1331554337
Type: single nucleotide variant
Location: chr17:44372414 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 1024: a β-strand

Full ITGA2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

platelet-type bleeding disorder 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITGA2B c.1545-1G>A Pathogenic ★★★ same condition
ITGA2B p.Arg584Ter Pathogenic ★★★ same condition
ITGA2B p.Arg977Ter Pathogenic ★★★ same condition
ITGA2B p.Asp591Ala Pathogenic ★★★ same condition
ITGA2B p.Gln778Pro Pathogenic ★★★ ⚠ same condition
ITGA2B p.Leu214Pro Pathogenic ★★★ same condition
ITGA2B p.Ala733Val Uncertain significance ★★★ ⚠ same condition
ITGA2B p.Arg1026Gln Uncertain significance ★★★ ⚠ 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/itga2b-p-phe1024ile (accessed [today's date]).

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