HTRA2 p.Asp386=
c.1158T>C · rs149488361 · VCV1948493
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
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 -0.55 | GERP 1.6, phastCons 0.076 |
| Overall | ||
| CADD | 7.552 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,890 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000372%
6/1,613,722 alleles · very rare
exomes 5/1,461,538 · genomes 1/152,184 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,890 |
| Finnishnot grpmax-eligible | 0.00156% | 64,034 |
| South Asian | 0.0011% | 91,046 |
| European (non-Finnish) | 0.000254% | 393,348 |
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.Asp386=
- Coding
- c.1158T>C
- MANE Select
- NM_013247
- dbSNP
- rs149488361
- Type
- single nucleotide variant
- Location
- chr2:74532661 (GRCh38)
- Gene constraint
- LOEUF 0.778 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.83 · 13 PDB
- Residue 386
- the pdz domain
Similar variants
- HTRA2 p.Asp386Asn Uncertain significance ★ ⚠ same residue
- HTRA2 p.Asp386Tyr Uncertain significance ⚠ same residue
- 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
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-asp386 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown