BHMT p.Phe74=
c.222C>T · rs35041410 · VCV711926
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.88%, 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 2.6 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 12.55 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.88%
African / African-American · 2,161/75,036 alleles
Filtering AF
2.78%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.74%
Overall
0.164%
2,652/1,614,152 alleles · low-frequency
exomes 1,382/1,461,816 · genomes 1,270/152,336 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.88% | 35 |
| Middle Eastern | 0.313% | 319 |
| Admixed American | 0.248% | 403 |
| Remaining individualsnot grpmax-eligible | 0.232% | 431 |
| Ashkenazi Jewishnot grpmax-eligible | 0.108% | 925 |
| European (non-Finnish) | 0.0116% | 8,613 |
| South Asian | 0.00988% | 10,120 |
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
- BHMT
- Protein
- p.Phe74=
- Coding
- c.222C>T
- MANE Select
- NM_001713
- dbSNP
- rs35041410
- Type
- single nucleotide variant
- Location
- chr5:79119314 (GRCh38)
- Gene constraint
- LOEUF 0.884 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.62 · 4 PDB
- Residue 74
- the hcy-binding domain
Similar variants
- BHMT p.Gly199Ser Benign/Likely benign ★★ same type
- BHMT p.Pro197Ser Benign ★★ same type
- BHMT p.Ala182Val Uncertain significance ★ ⚠ same type
- BHMT p.Ala210Thr Uncertain significance ★ same type
- BHMT p.Ala250Ser Uncertain significance ★ ⚠ same type
- BHMT p.Ala285Ser Uncertain significance ★ ⚠ same type
- BHMT p.Ala41Pro Uncertain significance ★ ⚠ same type
- BHMT p.Ala41Thr 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/bhmt-p-phe74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown