Is ITGA3 p.Thr486Met (c.1457C>T) pathogenic?

ITGA3 p.Thr486Met (c.1457C>T) is classified Uncertain significance in ITGA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-14). AlphaMissense: likely benign (0.209); Very rare (popmax 0.0022%, sas); Associated with Inborn genetic diseases.

What condition is associated with ITGA3 p.Thr486Met (c.1457C>T)?

ITGA3 p.Thr486Met (c.1457C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA3 p.Thr486Met (c.1457C>T) in the general population?

ITGA3 p.Thr486Met (c.1457C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about ITGA3 p.Thr486Met (c.1457C>T)?

AlphaMissense predicts likely benign (score 0.209) — an in-silico prediction, not a clinical call.

ITGA3 p.Thr486Met

c.1457C>T · VCV3861528

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.209	likely benign
REVEL	0.234	benign-leaning
SaProt	LLR -10.76	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	24.9	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 0.0022% South Asian · 2/91,028 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000372% 6/1,612,004 alleles · very rare exomes 6/1,459,674 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,514
Admixed American	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,446
European (non-Finnish)	0.00017%	589,116

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.Thr486Met
Coding: c.1457C>T
MANE Select: NM_002204
Type: single nucleotide variant
Location: chr17:50074522 (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.Thr486= 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-thr486met (accessed [today's date]).

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