Is ITGA3 p.Arg10His (c.29G>A) pathogenic?

ITGA3 p.Arg10His (c.29G>A) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-12). AlphaMissense: likely benign (0.1687); Ultra-rare (popmax 0.0407%, mid).

How common is ITGA3 p.Arg10His (c.29G>A) in the general population?

ITGA3 p.Arg10His (c.29G>A) is ultra-rare (popmax 0.0407%, mid) (gnomAD).

What do computational predictors say about ITGA3 p.Arg10His (c.29G>A)?

AlphaMissense predicts likely benign (score 0.1687) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg10His

c.29G>A · VCV3380498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1687 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0407%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1687	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -8.97	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 2.7	GERP -3.1, phastCons 0.13
Regional constraint	o/e 1.42	unconstrained · MANE · 54 bp · p 0.021 · regional, not allelic
Overall
CADD	12.61	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 0.0407% Middle Eastern · 2/4,912 alleles

Filtering AF 0.00717% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00299%

Overall 0.00026% 4/1,537,188 alleles · ultra-rare exomes 4/1,384,872 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0407%	2,456
European (non-Finnish)	0.000175%	570,832

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.Arg10His
Coding: c.29G>A
MANE Select: NM_002204
Type: single nucleotide variant
Location: chr17:50056468 (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 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
ITGA3 p.Ala1035Val Uncertain significance ★★ ⚠ same type
ITGA3 p.Arg156Trp 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-arg10his (accessed [today's date]).

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