MTHFR p.Val474=
c.1422G>A · VCV4881730
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.28 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.61 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 14.26 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- MTHFR
- Protein
- p.Val474=
- Coding
- c.1422G>A
- MANE Select
- NM_005957
- Type
- single nucleotide variant
- Location
- chr1:11794015 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.13 · 4 PDB
- Residue 474
- an α-helix
Similar variants
- MTHFR c.1166+1G>T Likely pathogenic ★★ same type
- MTHFR c.1166+5G>C Pathogenic/Likely pathogenic ★★ same type
- MTHFR c.1347+1G>A Pathogenic ★★ same type
- MTHFR c.1348-1G>C Likely pathogenic ★★ same type
- MTHFR c.1530+1G>A Likely pathogenic ★★ same type
- MTHFR c.1530+1G>T Likely pathogenic ★★ same type
- MTHFR c.1632+2T>G Pathogenic/Likely pathogenic ★★ same type
- MTHFR c.1752+1G>T Pathogenic/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/mthfr-p-val474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown