Is MTRFR p.Val41= (c.123C>A) pathogenic?

MTRFR p.Val41= (c.123C>A) is classified Likely benign in MTRFR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-28). Absent from gnomAD v4.1; Associated with combined oxidative phosphorylation defect type 7.

What condition is associated with MTRFR p.Val41= (c.123C>A)?

MTRFR p.Val41= (c.123C>A) is associated with combined oxidative phosphorylation defect type 7 (ClinVar).

How common is MTRFR p.Val41= (c.123C>A) in the general population?

MTRFR p.Val41= (c.123C>A) is absent from gnomAD v4.1 (gnomAD).

MTRFR p.Val41=

Q: How is Combined oxidative phosphorylation defect type 7 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.123C>A · rs2547597970 · VCV2937358

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

combined oxidative phosphorylation defect type 7

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 -1.5	GERP -1.9
Overall
CADD	1.044	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: MTRFR
Protein: p.Val41=
Coding: c.123C>A
MANE Select: NM_152269
dbSNP: rs2547597970
Type: single nucleotide variant
Location: chr12:123253797 (GRCh38)
Gene constraint: LOEUF 1.224 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.56 · 1 PDB

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

Disease context

combined oxidative phosphorylation defect type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 7 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MTRFR p.Arg132Ter Pathogenic ★★ same condition
MTRFR p.Arg15Ter Pathogenic/Likely pathogenic ★★ same condition
MTRFR c.*439C>T Uncertain significance ★★ same condition
MTRFR p.Ala145Thr Uncertain significance ★★ ⚠ same condition
MTRFR p.Ala19Val Uncertain significance ★★ ⚠ same condition
MTRFR p.Arg109Trp Uncertain significance ★★ ⚠ same condition
MTRFR p.Arg24Gln Uncertain significance ★★ ⚠ same condition
MTRFR p.Arg24Leu 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/mtrfr-p-val41 (accessed [today's date]).

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