HNMT p.Pro152=
c.456A>G · rs770593964 · VCV750363
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0018%, 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 2.2 | GERP 0.28, phastCons 1 |
| Overall | ||
| CADD | 9.868 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0018%
European (non-Finnish) · 21/1,164,902 alleles
Filtering AF
0.00116%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000983%
Overall
0.00138%
22/1,596,788 alleles · very rare
exomes 21/1,444,694 · genomes 1/152,094 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0018% | 55,471 |
| Finnishnot grpmax-eligible | 0.00156% | 64,008 |
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.Pro152=
- Coding
- c.456A>G
- MANE Select
- NM_006895
- dbSNP
- rs770593964
- Type
- single nucleotide variant
- Location
- chr2:138005158 (GRCh38)
- Gene constraint
- LOEUF 1.571 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 95.92 · 7 PDB
- Residue 152
- an α-helix
Similar variants
- HNMT p.Pro152Ser Uncertain significance ★ ⚠ same residue
- 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
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-pro152 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown