Is ITGA3 p.Arg549His (c.1646G>A) pathogenic?

ITGA3 p.Arg549His (c.1646G>A) is classified Uncertain significance in ITGA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.0802); Ultra-rare (popmax 0.0111%, eas).

How common is ITGA3 p.Arg549His (c.1646G>A) in the general population?

ITGA3 p.Arg549His (c.1646G>A) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

What do computational predictors say about ITGA3 p.Arg549His (c.1646G>A)?

AlphaMissense predicts likely benign (score 0.0802) — an in-silico prediction, not a clinical call.

ITGA3 p.Arg549His

c.1646G>A · rs557263701 · VCV2416077

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0802 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0802	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.32	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 0.067	GERP 0.53, phastCons 0.09
Regional constraint	o/e 0.84	unconstrained · MANE · 14 kb · p 6.1e-06 · regional, not allelic
Overall
CADD	18.19	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 0.0111% East Asian · 5/44,896 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.00118% 19/1,613,970 alleles · ultra-rare exomes 16/1,461,748 · genomes 3/152,222 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,979
South Asian	0.0022%	45,545
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000932%	107,271

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.Arg549His
Coding: c.1646G>A
MANE Select: NM_002204
dbSNP: rs557263701
Type: single nucleotide variant
Location: chr17:50075707 (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-arg549his (accessed [today's date]).

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