Is MTHFR p.Val507= (c.1521C>T) pathogenic?

MTHFR p.Val507= (c.1521C>T) is classified Likely benign in MTHFR (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-19). Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MTHFR p.Val507= (c.1521C>T)?

MTHFR p.Val507= (c.1521C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MTHFR p.Val507= (c.1521C>T) in the general population?

MTHFR p.Val507= (c.1521C>T) is absent from gnomAD v4.1 (gnomAD).

MTHFR p.Val507=

c.1521C>T · rs1035682753 · VCV2454056

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,607,150)

Conditions

Inborn genetic diseases

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 3.9	GERP 0.1, phastCons 1
Overall
CADD	8.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,607,150). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MTHFR
Protein: p.Val507=
Coding: c.1521C>T
MANE Select: NM_005957
dbSNP: rs1035682753
Type: single nucleotide variant
Location: chr1:11793916 (GRCh38)
Gene constraint: LOEUF 0.859 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.13 · 4 PDB
Residue 507: a β-strand

Full MTHFR gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTHFR p.Ala524Glu Uncertain significance ★★ ⚠ same condition
MTHFR p.Ala650Val Uncertain significance ★★ ⚠ same condition
MTHFR p.Arg535Pro Uncertain significance ★★ ⚠ same condition
MTHFR p.Arg606His Uncertain significance ★★ ⚠ same condition
MTHFR p.Asp629Gly Uncertain significance ★★ ⚠ same condition
MTHFR p.Gln267Lys Uncertain significance ★★ same condition
MTHFR p.Gly36Val Uncertain significance ★★ ⚠ same condition
MTHFR p.Gly87Asp 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-val507 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown