Is ITGA3 p.Val734Met (c.2200G>A) pathogenic?

ITGA3 p.Val734Met (c.2200G>A) is classified Conflicting classifications of pathogenicity in ITGA3 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-10-17). AlphaMissense: likely benign (0.2225); Rare (popmax 0.145%, nfe).

How common is ITGA3 p.Val734Met (c.2200G>A) in the general population?

ITGA3 p.Val734Met (c.2200G>A) is rare (popmax 0.145%, nfe) (gnomAD).

What do computational predictors say about ITGA3 p.Val734Met (c.2200G>A)?

AlphaMissense predicts likely benign (score 0.2225) — an in-silico prediction, not a clinical call.

ITGA3 p.Val734Met

c.2200G>A · rs139340161 · VCV1311930

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2225 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.145%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2225	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -12.14	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	20.7	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 0.145% European (non-Finnish) · 1,712/1,179,696 alleles

Filtering AF 0.139% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.115% 1,857/1,613,742 alleles · rare exomes 1,766/1,461,472 · genomes 91/152,270 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.145%	689
Remaining individualsnot grpmax-eligible	0.102%	976
Finnishnot grpmax-eligible	0.0937%	1,067
Admixed American	0.015%	6,667
African / African-American	0.0147%	6,821
South Asian	0.0011%	91,080

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.Val734Met
Coding: c.2200G>A
MANE Select: NM_002204
dbSNP: rs139340161
Type: single nucleotide variant
Location: chr17:50078106 (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-val734met (accessed [today's date]).

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