HTRA1 p.Ile172=
c.516C>A · VCV4689225
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00356%, nfe)
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 -5.5 | GERP -5 |
| Overall | ||
| CADD | 0.522 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00356%
European (non-Finnish) · 42/1,180,000 alleles
Filtering AF
0.00267%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00236%
Overall
0.00279%
45/1,614,030 alleles · very rare
exomes 41/1,461,830 · genomes 4/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00356% | 28,095 |
| African / African-American | 0.00267% | 37,468 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,474 |
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.Ile172=
- Coding
- c.516C>A
- MANE Select
- NM_002775
- Type
- single nucleotide variant
- Location
- chr10:122488945 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.30 · 18 PDB
- Residue 172
- an α-helix
Similar variants
- 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
- HTRA1 p.Arg302Ter Pathogenic/Likely pathogenic ★★ same type
- HTRA1 p.Arg370Ter 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-ile172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown