Is ITGA2B p.Lys709= (c.2127G>A) pathogenic?

ITGA2B p.Lys709= (c.2127G>A) is classified Benign in ITGA2B (ClinVar, Expert panel, 6 submitters; last evaluated 2019-09-18). Low-frequency (popmax 1.64%, afr); Associated with Glanzmann thrombasthenia.

What condition is associated with ITGA2B p.Lys709= (c.2127G>A)?

ITGA2B p.Lys709= (c.2127G>A) is associated with Glanzmann thrombasthenia (ClinVar).

How common is ITGA2B p.Lys709= (c.2127G>A) in the general population?

ITGA2B p.Lys709= (c.2127G>A) is low-frequency (popmax 1.64%, afr) (gnomAD).

How is Glanzmann thrombasthenia inherited?

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

ITGA2B p.Lys709=

c.2127G>A · rs114232872 · VCV323547

Benign Expert panel

Classification

Benign

ClinVar

Review

Expert panel ★★★☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.64%, afr)

Conditions

Glanzmann thrombasthenia

ClinGen expert panel — Platelet Disorders VCEP

Benign for Glanzmann's thrombasthenia. Applied ACMG criteria (verbatim):

BA1

Curation rationale (ClinGen, verbatim)

The Lys709= synonymous variant occurs at an allele frequency in gnomAD of 0.001729 with a MAF of 0.01699 (424/24,960 alleles) in the African population. This is above the >0.0024 threshold. This variant meets criteria to be classified as Benign by the ClinGen Platelet Disorders VCEP. GT-specific criteria met: BA1.

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

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 -0.59	GERP -3.1, phastCons 0.017
Overall
CADD	4.057	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.64% African / African-American · 1,230/75,014 alleles

Filtering AF 1.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.53%

Overall 0.0944% 1,524/1,613,950 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.64%	61
Admixed American	0.207%	484
Middle Eastern	0.149%	672
Remaining individualsnot grpmax-eligible	0.141%	710
European (non-Finnish)	0.00593%	16,856
South Asian	0.00329%	30,357

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.Lys709=
Coding: c.2127G>A
MANE Select: NM_000419
dbSNP: rs114232872
Type: single nucleotide variant
Location: chr17:44377758 (GRCh38)
Gene constraint: LOEUF 0.763 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.00 · 80 PDB
Residue 709: a disulfide bond

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 p.Lys709del Uncertain significance ★ same residue
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

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-lys709 (accessed [today's date]).

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