HNMT p.Ala92=
c.276T>C · rs767244384 · VCV3234771
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00678%, amr)
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 1.2 | GERP -1.6, phastCons 1 |
| Overall | ||
| CADD | 9.703 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00678%
Admixed American · 4/59,020 alleles
Filtering AF
0.00228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00136%
Overall
0.000249%
4/1,605,138 alleles · very rare
exomes 3/1,453,024 · genomes 1/152,114 · 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
- HNMT
- Protein
- p.Ala92=
- Coding
- c.276T>C
- MANE Select
- NM_006895
- dbSNP
- rs767244384
- Type
- single nucleotide variant
- Location
- chr2:138001003 (GRCh38)
- Gene constraint
- LOEUF 1.571 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.92 · 7 PDB
- Residue 92
- an α-helix
Similar variants
- HNMT p.Leu208Pro Likely pathogenic ★★ same type
- HNMT p.Gly48Ala Uncertain significance ★★ ⚠ same type
- HNMT p.Met1Ile Uncertain significance ★★ same type
- HNMT p.Gly60= Benign/Likely benign ★★ same type
- HNMT p.Tyr186= Likely benign ★★ same type
- HNMT p.Tyr147His Likely pathogenic ★ same type
- HNMT c.137+2287G>A Uncertain significance ★ same type
- HNMT p.Ala114Ser 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/hnmt-p-ala92 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown