Is ITGA3 p.Ser645Cys (c.1933A>T) pathogenic?

ITGA3 p.Ser645Cys (c.1933A>T) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-09). AlphaMissense: ambiguous (0.4637); Very rare (popmax 0.000425%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ITGA3 p.Ser645Cys (c.1933A>T)?

ITGA3 p.Ser645Cys (c.1933A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA3 p.Ser645Cys (c.1933A>T) in the general population?

ITGA3 p.Ser645Cys (c.1933A>T) is very rare (popmax 0.000425%, nfe) (gnomAD).

What do computational predictors say about ITGA3 p.Ser645Cys (c.1933A>T)?

AlphaMissense predicts ambiguous (score 0.4637) — an in-silico prediction, not a clinical call.

ITGA3 p.Ser645Cys

c.1933A>T · rs774823234 · VCV2388386

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4637 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000425%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4637	ambiguous
REVEL	0.316	indeterminate
SaProt	LLR -11.37	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.71, phastCons 0.92
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	22.3	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 0.000425% European (non-Finnish) · 5/1,177,272 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.000311% 5/1,609,656 alleles · very rare exomes 5/1,457,386 · genomes 0/152,270 · joint denominator

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.Ser645Cys
Coding: c.1933A>T
MANE Select: NM_002204
dbSNP: rs774823234
Type: single nucleotide variant
Location: chr17:50076984 (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.Ser645Ile Uncertain significance ★ ⚠ 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-ser645cys (accessed [today's date]).

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