ITGA3 p.Ser666=
c.1998C>T · VCV4694240
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00443%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.041 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.82 | GERP -3, phastCons 0.008 |
| Overall | ||
| CADD | 6.804 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00443%
South Asian · 4/90,288 alleles
Filtering AF
0.00143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000897%
Overall
0.000311%
5/1,607,114 alleles · very rare
exomes 5/1,454,978 · genomes 0/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00443% | 22,572 |
| European (non-Finnish) | 8.5e-05% | 1,176,482 |
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.Ser666=
- Coding
- c.1998C>T
- MANE Select
- NM_002204
- Type
- single nucleotide variant
- Location
- chr17:50077049 (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-ser666 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown