Is ITGA3 p.Gly533Ser (c.1597G>A) pathogenic?

ITGA3 p.Gly533Ser (c.1597G>A) is classified Uncertain significance in ITGA3 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0975); Very rare (popmax 0.00737%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ITGA3 p.Gly533Ser (c.1597G>A)?

ITGA3 p.Gly533Ser (c.1597G>A) is associated with Inborn genetic diseases, epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome (ClinVar).

How common is ITGA3 p.Gly533Ser (c.1597G>A) in the general population?

ITGA3 p.Gly533Ser (c.1597G>A) is very rare (popmax 0.00737%, nfe) (gnomAD).

What do computational predictors say about ITGA3 p.Gly533Ser (c.1597G>A)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

ITGA3 p.Gly533Ser

c.1597G>A · rs377600580 · VCV1347927

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00737%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -8.13	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 0.86	GERP -3.8
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	5.934	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00737% European (non-Finnish) · 87/1,180,058 alleles

Filtering AF 0.00605% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00565%

Overall 0.00589% 95/1,614,100 alleles · very rare exomes 90/1,461,848 · genomes 5/152,252 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00737%	13,564
African / African-American	0.004%	24,979
South Asian	0.00329%	30,363
East Asian	0.00223%	44,894
Admixed American	0.00167%	60,012

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.Gly533Ser
Coding: c.1597G>A
MANE Select: NM_002204
dbSNP: rs377600580
Type: single nucleotide variant
Location: chr17:50075658 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa, junctional 7, with interstitial lung disease and nephrotic syndrome

Similar variants

ITGA3 p.Gly533Cys Uncertain significance ★ ⚠ same residue
ITGA3 c.2070+1G>A Pathogenic ★★ same condition
ITGA3 p.Arg274Gln Likely pathogenic ★★ ⚠ same condition
ITGA3 p.Arg875Ter Likely pathogenic ★★ same condition
ITGA3 c.*48G>A Uncertain significance ★★ same condition
ITGA3 c.*96G>A Uncertain significance ★★ same condition
ITGA3 p.Ala1026Val Uncertain significance ★★ ⚠ same condition
ITGA3 p.Ala1035Val Uncertain significance ★★ ⚠ 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-gly533ser (accessed [today's date]).

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