HTRA1 p.Pro475=
c.1425C>T · rs779158785 · VCV756342
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -11 | GERP -4.4 |
| Overall | ||
| CADD | 4.726 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/59,992 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.00149%
24/1,613,954 alleles · very rare
exomes 23/1,461,850 · genomes 1/152,104 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 19,997 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,606 |
| Finnishnot grpmax-eligible | 0.00312% | 32,014 |
| East Asian | 0.00223% | 44,894 |
| South Asian | 0.0022% | 45,536 |
| African / African-American | 0.00134% | 74,888 |
| European (non-Finnish) | 0.00119% | 84,286 |
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
- HTRA1
- Protein
- p.Pro475=
- Coding
- c.1425C>T
- MANE Select
- NM_002775
- dbSNP
- rs779158785
- Type
- single nucleotide variant
- Location
- chr10:122514341 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.30 · 18 PDB
Similar variants
- HTRA1 p.Pro475Ala Uncertain significance ★★ same residue
- HTRA1 p.Pro475Ser Uncertain significance ★ ⚠ same residue
- HTRA1 c.972+1G>A Pathogenic/Likely pathogenic ★★ same type
- HTRA1 p.Arg166Cys Pathogenic/Likely pathogenic ★★ same type
- HTRA1 p.Arg166His Pathogenic/Likely pathogenic ★★ same type
- HTRA1 p.Arg166Leu Pathogenic ★★ same type
- HTRA1 p.Arg274Gln Pathogenic/Likely pathogenic ★★ same type
- HTRA1 p.Arg302Gln Pathogenic/Likely pathogenic ★★ 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/htra1-p-pro475 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown