Is ITGA3 p.Ser741= (c.2223G>A) pathogenic?

ITGA3 p.Ser741= (c.2223G>A) is classified Likely benign in ITGA3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-08-03). Very rare (popmax 0.00134%, afr); Associated with ITGA3-related disorder.

What condition is associated with ITGA3 p.Ser741= (c.2223G>A)?

ITGA3 p.Ser741= (c.2223G>A) is associated with ITGA3-related disorder (ClinVar).

How common is ITGA3 p.Ser741= (c.2223G>A) in the general population?

ITGA3 p.Ser741= (c.2223G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

ITGA3 p.Ser741=

c.2223G>A · rs759678196 · VCV3032641

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

ITGA3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.229	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.004	GERP -3.6, phastCons 0.068
Overall
CADD	3.581	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,894 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000682% 11/1,613,860 alleles · very rare exomes 8/1,461,762 · genomes 3/152,098 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,894
European (non-Finnish)	0.000847%	117,995

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.Ser741=
Coding: c.2223G>A
MANE Select: NM_002204
dbSNP: rs759678196
Type: single nucleotide variant
Location: chr17:50078210 (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

ITGA3-related disorder

Similar variants

ITGA3 p.Arg276Ter Likely pathogenic ★ same condition
ITGA3 p.Arg932Ter Likely pathogenic ★ same condition
ITGA3 p.Gln348Ter Likely pathogenic ★ same condition
ITGA3 p.Asp36Tyr Uncertain significance ★ ⚠ same condition
ITGA3 p.Pro506Thr Uncertain significance ⚠ same condition
ITGA3 c.1537+8C>A Likely benign same condition
ITGA3 c.2706+9C>T Likely benign same condition
ITGA3 p.Ala312= Likely benign 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-ser741 (accessed [today's date]).

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