Is ITGA3 p.Arg525Trp (c.1573C>T) pathogenic?

ITGA3 p.Arg525Trp (c.1573C>T) is classified Uncertain significance in ITGA3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-21). AlphaMissense: likely benign (0.1644); Ultra-rare (popmax 0.066%, mid); Associated with Inborn genetic diseases.

What condition is associated with ITGA3 p.Arg525Trp (c.1573C>T)?

ITGA3 p.Arg525Trp (c.1573C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ITGA3 p.Arg525Trp (c.1573C>T) in the general population?

ITGA3 p.Arg525Trp (c.1573C>T) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about ITGA3 p.Arg525Trp (c.1573C>T)?

AlphaMissense predicts likely benign (score 0.1644) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg525Trp

c.1573C>T · rs370814972 · VCV2267531

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1644 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1644	likely benign
REVEL	0.334	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.99, phastCons 0.35
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	24.3	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 0.066% Middle Eastern · 4/6,062 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00502% 81/1,614,230 alleles · ultra-rare exomes 73/1,461,848 · genomes 8/152,382 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,516
East Asian	0.00668%	14,961
European (non-Finnish)	0.00559%	17,880
Admixed American	0.005%	20,011
Remaining individualsnot grpmax-eligible	0.0032%	31,256
African / African-American	0.00266%	37,536
South Asian	0.0011%	91,084

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.Arg525Trp
Coding: c.1573C>T
MANE Select: NM_002204
dbSNP: rs370814972
Type: single nucleotide variant
Location: chr17:50075634 (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

Similar variants

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ITGA3 p.Gly533Ser Uncertain significance ★★ ⚠ same condition
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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-arg525trp (accessed [today's date]).

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