HTRA2 p.Ala113=
c.339T>C · VCV3605201
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00135%, afr)
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 -0.84 | GERP -3.4, phastCons 0.011 |
| Overall | ||
| CADD | 8.323 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00135%
African / African-American · 1/74,000 alleles
Filtering AF
0.000185%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000122%
Overall
0.00044%
7/1,590,622 alleles · very rare
exomes 5/1,439,290 · genomes 2/151,332 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00135% | 74,000 |
| European (non-Finnish) | 0.000514% | 194,551 |
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
- HTRA2
- Protein
- p.Ala113=
- Coding
- c.339T>C
- MANE Select
- NM_013247
- Type
- single nucleotide variant
- Location
- chr2:74530345 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.83 · 13 PDB
Similar variants
- HTRA2 p.Arg380Ter Pathogenic ★★ same type
- HTRA2 p.Gln82Ter Pathogenic ★★ same type
- AUP1 p.Pro9Ser Uncertain significance ★★ ⚠ same type
- HTRA2 c.507-10T>A Uncertain significance ★★ same type
- HTRA2 c.507-9C>A Uncertain significance ★★ same type
- HTRA2 p.Ala110Gly Uncertain significance ★★ ⚠ same type
- HTRA2 p.Ala415Thr Uncertain significance ★★ ⚠ same type
- HTRA2 p.Arg252Gln 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/htra2-p-ala113 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown