ITGA3 p.Pro546=
c.1638C>T · rs537585938 · VCV2903335
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -3.8 |
| Overall | ||
| CADD | 0.018 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,930 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00228%
Overall
0.0013%
21/1,614,022 alleles · very rare
exomes 19/1,461,804 · genomes 2/152,218 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00801% | 12,488 |
| East Asian | 0.00223% | 44,892 |
| South Asian | 0.0022% | 45,545 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| European (non-Finnish) | 0.000932% | 107,273 |
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.Pro546=
- Coding
- c.1638C>T
- MANE Select
- NM_002204
- dbSNP
- rs537585938
- Type
- single nucleotide variant
- Location
- chr17:50075699 (GRCh38)
- Gene constraint
- LOEUF 0.69 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.88
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-pro546 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown