HEPHL1 p.Pro95=
c.285C>G · rs2496186281 · VCV2642290
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 6.2e-05%)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.39 | GERP 0.068, phastCons 0.84 |
| Overall | ||
| CADD | 8.41 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.2e-05%
Overall
6.2e-05%
1/1,613,960 alleles · very rare
exomes 1/1,461,638 · genomes 0/152,322 · joint denominator
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
- HEPHL1
- Protein
- p.Pro95=
- Coding
- c.285C>G
- MANE Select
- NM_001098672
- dbSNP
- rs2496186281
- Type
- single nucleotide variant
- Location
- chr11:94045787 (GRCh38)
- Gene constraint
- LOEUF 1.145 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.76
- Residue 95
- the plastocyanin-like 1 domain
Similar variants
- HEPHL1 p.Arg1021Gly Uncertain significance ★★ ⚠ same type
- HEPHL1 p.Asn990His Uncertain significance ★★ ⚠ same type
- HEPHL1 c.1232+9C>G Benign ★★ same type
- HEPHL1 c.3046-35G>T Benign ★★ same type
- HEPHL1 p.Asn251Asp Benign ★★ same type
- HEPHL1 p.Phe754= Benign/Likely benign ★★ same type
- HEPHL1 p.Pro1090= Likely benign ★★ same type
- HEPHL1 p.Pro869= Likely benign ★★ 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/hephl1-p-pro95 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown