Is ITGA3 p.Asp592Glu (c.1776C>A) pathogenic?

ITGA3 p.Asp592Glu (c.1776C>A) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-26). AlphaMissense: ambiguous (0.3517); Very rare (popmax 8.47e-05%, nfe).

How common is ITGA3 p.Asp592Glu (c.1776C>A) in the general population?

ITGA3 p.Asp592Glu (c.1776C>A) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ITGA3 p.Asp592Glu (c.1776C>A)?

AlphaMissense predicts ambiguous (score 0.3517) — an in-silico prediction, not a clinical call.

ITGA3 p.Asp592Glu

c.1776C>A · rs147491290 · VCV1964839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3517 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3517	ambiguous
REVEL	0.193	benign-leaning
SaProt	LLR -5.16	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.4	GERP -1.5
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	18.1	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 8.47e-05% European (non-Finnish) · 1/1,180,000 alleles

Overall 6.21e-05% 1/1,611,506 alleles · very rare exomes 0/1,459,208 · genomes 1/152,298 · 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.Asp592Glu
Coding: c.1776C>A
MANE Select: NM_002204
dbSNP: rs147491290
Type: single nucleotide variant
Location: chr17:50076427 (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 p.Asp592= Likely benign ★ same residue
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

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-asp592glu (accessed [today's date]).

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