Is ITGA2B p.Arg993= (c.2979G>A) pathogenic?

ITGA2B p.Arg993= (c.2979G>A) is classified Likely benign in ITGA2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). Very rare (popmax 0.00333%, amr); Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Arg993= (c.2979G>A)?

ITGA2B p.Arg993= (c.2979G>A) is associated with Glanzmann thrombasthenia (ClinVar).

How common is ITGA2B p.Arg993= (c.2979G>A) in the general population?

ITGA2B p.Arg993= (c.2979G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

How is Glanzmann thrombasthenia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ITGA2B p.Arg993=

c.2979G>A · rs1478125843 · VCV2792131

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Glanzmann thrombasthenia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.24 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.21	GERP -2.4
Overall
CADD	7.128	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,022 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000124% 2/1,614,154 alleles · very rare exomes 2/1,461,874 · genomes 0/152,280 · 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: ITGA2B
Protein: p.Arg993=
Coding: c.2979G>A
MANE Select: NM_000419
dbSNP: rs1478125843
Type: single nucleotide variant
Location: chr17:44374435 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 993: a turn

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

Disease context

Glanzmann thrombasthenia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glanzmann thrombasthenia (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ITGA2B c.1210+105A>G Likely pathogenic ★★★ same condition
ITGA2B c.1210+5G>A Likely pathogenic ★★★ same condition
ITGA2B c.1211-1G>C Likely pathogenic ★★★ same condition
ITGA2B c.1544+1G>A Pathogenic ★★★ same condition
ITGA2B c.1545-1G>A Pathogenic ★★★ same condition
ITGA2B c.1600+1G>A Pathogenic ★★★ same condition
ITGA2B c.1752+2T>C Pathogenic ★★★ same condition
ITGA2B c.1753-1G>A 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/itga2b-p-arg993 (accessed [today's date]).

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