MTHFS p.Ala172=
c.516G>C · rs754470226 · VCV2766468
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000169%, 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 1 | GERP -2.1, phastCons 0.93 |
| Overall | ||
| CADD | 5.786 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000169%
European (non-Finnish) · 2/1,180,022 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000124%
2/1,614,140 alleles · very rare
exomes 2/1,461,880 · genomes 0/152,260 · 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
- MTHFS
- Protein
- p.Ala172=
- Coding
- c.516G>C
- MANE Select
- NM_006441
- dbSNP
- rs754470226
- Type
- single nucleotide variant
- Location
- chr15:79845306 (GRCh38)
- Gene constraint
- LOEUF 0.992 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 95.35 · 4 PDB
- Residue 172
- a UniProt-annotated variant site (in nedmehm); a β-strand
Similar variants
- MTHFS p.Ser12Ile Uncertain significance ★★ ⚠ same type
- MTHFS c.117+7G>C Benign/Likely benign ★★ same type
- MTHFS p.Asp140= Benign ★★ same type
- MTHFS p.Lys18= Benign/Likely benign ★★ same type
- MTHFS p.Arg74Ter Pathogenic ★ same type
- MTHFS p.Gln162Ter Likely pathogenic ★ same type
- MTHFS p.Lys106Ter Pathogenic ★ same type
- MTHFS p.Tyr153Cys Likely pathogenic ★ 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/mthfs-p-ala172 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown