Is ITGA3 p.Arg461Gln (c.1382G>A) pathogenic?

ITGA3 p.Arg461Gln (c.1382G>A) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-09-01). AlphaMissense: ambiguous (0.4984); Very rare (popmax 0.00133%, afr).

How common is ITGA3 p.Arg461Gln (c.1382G>A) in the general population?

ITGA3 p.Arg461Gln (c.1382G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ITGA3 p.Arg461Gln (c.1382G>A)?

AlphaMissense predicts ambiguous (score 0.4984) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg461Gln

c.1382G>A · rs772057144 · VCV1701324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4984 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4984	ambiguous
REVEL	0.88	moderately pathogenic-leaning
SaProt	LLR -11.73	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.74	donor loss · deltas
Pangolin	Δ0.70	loss · gain 0.07 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	35.0	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 0.00133% African / African-American · 1/74,916 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000558% 9/1,613,726 alleles · very rare exomes 8/1,461,538 · genomes 1/152,188 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	74,916
South Asian	0.0011%	91,020
European (non-Finnish)	0.000593%	168,554

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.Arg461Gln
Coding: c.1382G>A
MANE Select: NM_002204
dbSNP: rs772057144
Type: single nucleotide variant
Location: chr17:50074280 (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 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
ITGA3 p.Arg156Trp 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-arg461gln (accessed [today's date]).

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