HTRA1 p.Pro48=
c.144G>T · rs565162637 · VCV798282
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0107%, 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 2.3 | GERP -1.9, phastCons 0.3 |
| Overall | ||
| CADD | 12.11 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0107%
European (non-Finnish) · 94/877,530 alleles
Filtering AF
0.00893%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00829%
Overall
0.00929%
98/1,054,602 alleles · ultra-rare
exomes 85/907,584 · genomes 13/147,018 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0107% | 9,335 |
| Remaining individualsnot grpmax-eligible | 0.00595% | 16,793 |
| Admixed American | 0.00541% | 18,468 |
| South Asian | 0.00424% | 23,604 |
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.Pro48=
- Coding
- c.144G>T
- MANE Select
- NM_002775
- dbSNP
- rs565162637
- Type
- single nucleotide variant
- Location
- chr10:122461796 (GRCh38)
- Gene constraint
- LOEUF 0.873 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 83.30 · 18 PDB
- Residue 48
- the igfbp n-terminal domain; 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-pro48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown