MTHFD1 p.Pro887=
c.2661C>T · rs759391345 · VCV2176279
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00161%, 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 2.8 | GERP 1.4, phastCons 1 |
| Overall | ||
| CADD | 10.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00161%
European (non-Finnish) · 19/1,180,032 alleles
Filtering AF
0.00103%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00083%
Overall
0.00118%
19/1,614,206 alleles · very rare
exomes 19/1,461,872 · genomes 0/152,334 · 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
- MTHFD1
- Protein
- p.Pro887=
- Coding
- c.2661C>T
- MANE Select
- NM_005956
- dbSNP
- rs759391345
- Type
- single nucleotide variant
- Location
- chr14:64454818 (GRCh38)
- Gene constraint
- LOEUF 0.51 · pLI 0.83 (gnomAD)
- Structure
- AlphaFold pLDDT 94.63 · 12 PDB
- Residue 887
- a UniProt-annotated variant site (in cimah); the 'formyltetrahydrofolate synthetase 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-pro887 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown