Is ITGA3 p.Arg293Gln (c.878G>A) pathogenic?

ITGA3 p.Arg293Gln (c.878G>A) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0639); Ultra-rare (popmax 0.0165%, mid).

How common is ITGA3 p.Arg293Gln (c.878G>A) in the general population?

ITGA3 p.Arg293Gln (c.878G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about ITGA3 p.Arg293Gln (c.878G>A)?

AlphaMissense predicts likely benign (score 0.0639) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg293Gln

c.878G>A · rs546685892 · VCV1921910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0639 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0639	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.37	GERP -1.6, phastCons 0.001
Regional constraint	o/e 0.67	unconstrained · MANE · 18 kb · p 5.2e-14 · regional, not allelic
Overall
CADD	14.83	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,046 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000991% 16/1,614,028 alleles · ultra-rare exomes 14/1,461,674 · genomes 2/152,354 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,046
South Asian	0.0022%	45,545
Admixed American	0.00167%	60,030
African / African-American	0.00133%	75,056
European (non-Finnish)	0.000932%	107,277

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: ITGA3
Protein: p.Arg293Gln
Coding: c.878G>A
MANE Select: NM_002204
dbSNP: rs546685892
Type: single nucleotide variant
Location: chr17:50071437 (GRCh38)
Gene constraint: LOEUF 0.69 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.88

Full ITGA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ITGA3 p.Arg293Trp Uncertain significance ★★ ⚠ same residue
ITGA3 p.Arg293= Likely benign ★ same residue
ITGA3 c.2070+1G>A Pathogenic ★★ same type
ITGA3 p.Arg274Gln Likely pathogenic ★★ ⚠ same type
ITGA3 p.Arg875Ter Likely pathogenic ★★ same type
ITGA3 c.*48G>A Uncertain significance ★★ same type
ITGA3 c.*96G>A Uncertain significance ★★ same type
ITGA3 p.Ala1026Val Uncertain significance ★★ ⚠ same type

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/itga3-p-arg293gln (accessed [today's date]).

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