MTHFR p.Asn537fs
c.1610_1613del · VCV4815467
Likely pathogenic
Single submitter
Classification
Likely pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
Conditions
1
homocystinuria due to methylene tetrahydrofolate reductase deficiency
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | frameshift | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 10 of 12 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.2 | GERP 0.3, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- MTHFR
- Protein
- p.Asn537fs
- Coding
- c.1610_1613del
- MANE Select
- NM_005957
- Type
- Deletion
- Location
- chr1:11792297 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.13 · 4 PDB
- Residue 537
- a β-strand
Disease context
homocystinuria due to methylene tetrahydrofolate reductase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Homocystinuria due to methylene tetrahydrofolate reductase deficiency (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Infancy, Neonatal
Similar variants
- MTHFR p.Asn537= Likely benign ★ same residue
- MTHFR c.1167-2del Pathogenic ★★ same condition
- MTHFR p.Asp38fs Likely pathogenic ★★ same condition
- MTHFR p.Ile287fs Pathogenic/Likely pathogenic ★★ same condition
- MTHFR p.Ile497fs Pathogenic/Likely pathogenic ★★ same condition
- MTHFR p.Leu590fs Pathogenic ★★ same condition
- MTHFR p.Ser410_Lys414del Pathogenic/Likely pathogenic ★★ same condition
- MTHFR p.Lys215del Uncertain significance ★★ same condition
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-asn537fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown