STRA6 p.Val197=
c.591G>A · rs138499753 · VCV767298
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0552%, mid)
Conditions
1
microphthalmia, syndromic 9
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Pangolin | Δ0.22 | gain · loss 0.03 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP -4.4 | GERP -4.3 |
| Overall | ||
| CADD | 0.462 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0552%
Middle Eastern · 3/5,432 alleles
Filtering AF
0.015%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.008%
Overall
0.00763%
123/1,612,412 alleles · ultra-rare
exomes 113/1,460,126 · genomes 10/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0552% | 1,811 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,241 |
| Admixed American | 0.0133% | 7,497 |
| European (non-Finnish) | 0.00822% | 12,164 |
| African / African-American | 0.00533% | 18,750 |
| South Asian | 0.0011% | 90,908 |
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
- STRA6
- Protein
- p.Val197=
- Coding
- c.591G>A
- MANE Select
- NM_022369
- dbSNP
- rs138499753
- Type
- single nucleotide variant
- Location
- chr15:74195308 (GRCh38)
- Gene constraint
- LOEUF 0.725 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 78.18
Similar variants
- STRA6 c.267-1G>T Pathogenic/Likely pathogenic ★★ same condition
- STRA6 p.Arg532Ter Pathogenic ★★ same condition
- STRA6 p.Thr644Met Pathogenic ★★ ⚠ same condition
- STRA6 c.*10A>C Uncertain significance ★★ same condition
- STRA6 p.Ala54Ser Uncertain significance ★★ ⚠ same condition
- STRA6 p.Ala557Val Uncertain significance ★★ ⚠ same condition
- STRA6 p.Arg467Cys Uncertain significance ★★ ⚠ same condition
- STRA6 p.Arg655Cys 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/stra6-p-val197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown