MTHFS p.Ser200=
c.600G>A · VCV3710793
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0773%, 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 -1.1 | GERP -2.9 |
| Overall | ||
| CADD | 2.92 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0773%
African / African-American · 58/75,046 alleles
Filtering AF
0.0613%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0556%
Overall
0.00836%
135/1,614,158 alleles · ultra-rare
exomes 104/1,461,868 · genomes 31/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0773% | 1,294 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,930 |
| Admixed American | 0.00833% | 12,005 |
| European (non-Finnish) | 0.00508% | 19,667 |
| South Asian | 0.00439% | 22,772 |
| East Asian | 0.00223% | 44,886 |
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.Ser200=
- Coding
- c.600G>A
- MANE Select
- NM_006441
- Type
- single nucleotide variant
- Location
- chr15:79845222 (GRCh38)
- Gene constraint
- LOEUF 0.992 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 95.35 · 4 PDB
- Residue 200
- a UniProt-annotated variant site (in nedmehm)
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-ser200 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown