Is ITGA3 p.Arg76Trp (c.226C>T) pathogenic?

ITGA3 p.Arg76Trp (c.226C>T) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.2174); Ultra-rare (popmax 0.0187%, afr); Associated with Inborn genetic diseases.

What condition is associated with ITGA3 p.Arg76Trp (c.226C>T)?

ITGA3 p.Arg76Trp (c.226C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA3 p.Arg76Trp (c.226C>T) in the general population?

ITGA3 p.Arg76Trp (c.226C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about ITGA3 p.Arg76Trp (c.226C>T)?

AlphaMissense predicts likely benign (score 0.2174) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg76Trp

c.226C>T · rs142527278 · VCV2514406

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2174 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2174	likely benign
REVEL	0.571	indeterminate
SaProt	LLR -11.47	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 0.64, phastCons 0.82
Regional constraint	o/e 0.67	unconstrained · MANE · 18 kb · p 5.2e-14 · regional, not allelic
Overall
CADD	28.7	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

Grpmax group 0.0187% African / African-American · 14/74,956 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00205% 33/1,612,660 alleles · ultra-rare exomes 24/1,460,506 · genomes 9/152,154 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,354
South Asian	0.0143%	6,975
Remaining individualsnot grpmax-eligible	0.0016%	62,414
European (non-Finnish)	0.000424%	235,943

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.Arg76Trp
Coding: c.226C>T
MANE Select: NM_002204
dbSNP: rs142527278
Type: single nucleotide variant
Location: chr17:50064096 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITGA3 p.Arg76Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
ITGA3 p.Arg293Trp Uncertain significance ★★ ⚠ same condition
ITGA3 p.Arg524His Uncertain significance ★★ ⚠ same condition
ITGA3 p.Arg525Trp Uncertain significance ★★ ⚠ same condition
ITGA3 p.Arg589Pro Uncertain significance ★★ ⚠ same condition
ITGA3 p.Arg932Gln Uncertain significance ★★ ⚠ same condition
ITGA3 p.Glu668Asp Uncertain significance ★★ same condition
ITGA3 p.Gly533Ser 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/itga3-p-arg76trp (accessed [today's date]).

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