MTHFD1 p.Pro162=
c.486G>A · rs747448137 · VCV2191265
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0203%, mid)
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 4.4 | GERP -0.03, phastCons 1 |
| Overall | ||
| CADD | 12.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0203%
Middle Eastern · 1/4,924 alleles
Filtering AF
0.00726%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00514%
Overall
0.00124%
20/1,612,488 alleles · ultra-rare
exomes 19/1,460,338 · genomes 1/152,150 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0203% | 4,924 |
| East Asian | 0.0156% | 6,414 |
| Admixed American | 0.00834% | 11,998 |
| South Asian | 0.0011% | 91,012 |
| European (non-Finnish) | 0.000508% | 196,658 |
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
- MTHFD1
- Protein
- p.Pro162=
- Coding
- c.486G>A
- MANE Select
- NM_005956
- dbSNP
- rs747448137
- Type
- single nucleotide variant
- Location
- chr14:64417895 (GRCh38)
- Gene constraint
- LOEUF 0.51 · pLI 0.83 (gnomAD)
- Structure
- AlphaFold pLDDT 94.63 · 12 PDB
- Residue 162
- a UniProt-annotated variant site (in); the 'methylenetetrahydrofolate dehydrogenase and methenyltetrahydrofolate cyclohydrolase (d/c) domain' region
Similar variants
- MTHFD1 c.727+1G>A Pathogenic/Likely pathogenic ★★ same type
- MTHFD1 p.Arg173Cys Pathogenic/Likely pathogenic ★★ same type
- MTHFD1 p.Gln100Ter Likely pathogenic ★★ same type
- MTHFD1 p.Glu225Ter Pathogenic ★★ same type
- MTHFD1 p.Ser49Phe Pathogenic/Likely pathogenic ★★ same type
- MTHFD1 c.186+5C>T Uncertain significance ★★ same type
- MTHFD1 p.Arg173His Uncertain significance ★★ ⚠ same type
- MTHFD1 p.Arg293Cys 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/mthfd1-p-pro162 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown