Is ITGA3 p.Leu371Phe (c.1113A>T) pathogenic?

ITGA3 p.Leu371Phe (c.1113A>T) is classified Benign/Likely benign in ITGA3 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0459); Common (popmax 5.13%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about ITGA3 p.Leu371Phe (c.1113A>T)?

AlphaMissense predicts likely benign (score 0.0459) — an in-silico prediction, not a clinical call.

ITGA3 p.Leu371Phe

Q: How common is ITGA3 p.Leu371Phe (c.1113A>T) in the general population?

ITGA3 p.Leu371Phe (c.1113A>T) is common (popmax 5.13%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1113A>T · rs61730085 · VCV783785

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0459 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 5.13%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0459	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -7.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.77	GERP -1.3, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 18 kb · p 5.2e-14 · regional, not allelic
Overall
CADD	2.8	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 5.13% African / African-American · 3,845/74,958 alleles

Filtering AF 4.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.94%

Overall 0.288% 4,650/1,613,852 alleles · common exomes 2,461/1,461,722 · genomes 2,189/152,130 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.13%	19
Admixed American	0.403%	248
Remaining individualsnot grpmax-eligible	0.381%	263
Middle Eastern	0.285%	351
European (non-Finnish)	0.0253%	3,960
South Asian	0.011%	9,107

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.Leu371Phe
Coding: c.1113A>T
MANE Select: NM_002204
dbSNP: rs61730085
Type: single nucleotide variant
Location: chr17:50072139 (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-leu371phe (accessed [today's date]).

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