Is ITGA3 p.Thr429Ile (c.1286C>T) pathogenic?

ITGA3 p.Thr429Ile (c.1286C>T) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: ambiguous (0.4648); Ultra-rare (popmax 0.0285%, sas); Associated with Inborn genetic diseases.

What condition is associated with ITGA3 p.Thr429Ile (c.1286C>T)?

ITGA3 p.Thr429Ile (c.1286C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA3 p.Thr429Ile (c.1286C>T) in the general population?

ITGA3 p.Thr429Ile (c.1286C>T) is ultra-rare (popmax 0.0285%, sas) (gnomAD).

What do computational predictors say about ITGA3 p.Thr429Ile (c.1286C>T)?

AlphaMissense predicts ambiguous (score 0.4648) — an in-silico prediction, not a clinical call.

ITGA3 p.Thr429Ile

c.1286C>T · rs575130011 · VCV2283565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4648 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0285%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4648	ambiguous
REVEL	0.518	indeterminate
SaProt	LLR -11.85	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 0.69, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	25.2	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 0.0285% South Asian · 26/91,082 alleles

Filtering AF 0.0199% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00248% 40/1,614,204 alleles · ultra-rare exomes 39/1,461,882 · genomes 1/152,322 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.000678%	147,505

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.Thr429Ile
Coding: c.1286C>T
MANE Select: NM_002204
dbSNP: rs575130011
Type: single nucleotide variant
Location: chr17:50074184 (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.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
ITGA3 p.Leu410Phe 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-thr429ile (accessed [today's date]).

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