Is MTFMT p.Arg7Gly (c.19C>G) pathogenic?

MTFMT p.Arg7Gly (c.19C>G) is classified Uncertain significance in MTFMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0787); Very rare (popmax 0.00127%, nfe); Associated with combined oxidative phosphorylation defect type 15.

What condition is associated with MTFMT p.Arg7Gly (c.19C>G)?

MTFMT p.Arg7Gly (c.19C>G) is associated with combined oxidative phosphorylation defect type 15 (ClinVar).

How common is MTFMT p.Arg7Gly (c.19C>G) in the general population?

MTFMT p.Arg7Gly (c.19C>G) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about MTFMT p.Arg7Gly (c.19C>G)?

AlphaMissense predicts likely benign (score 0.0787) — an in-silico prediction, not a clinical call.

MTFMT p.Arg7Gly

Q: How is Combined oxidative phosphorylation defect type 15 inherited?

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

c.19C>G · rs759489465 · VCV548003

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0787 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined oxidative phosphorylation defect type 15

Computational evidence

Protein change
AlphaMissense	0.0787	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -6.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.3
Regional constraint	o/e 1.06	unconstrained · MANE · 27 kb · p 0.18 · regional, not allelic
Overall
CADD	0.266	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00127% European (non-Finnish) · 14/1,099,640 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000578%

Overall 0.00103% 15/1,452,192 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00181%	55,376
European (non-Finnish)grpmax	0.00127%	78,546

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MTFMT
Protein: p.Arg7Gly
Coding: c.19C>G
MANE Select: NM_139242
dbSNP: rs759489465
Type: single nucleotide variant
Location: chr15:65029595 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.08

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

Disease context

combined oxidative phosphorylation defect type 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined oxidative phosphorylation defect type 15 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MTFMT p.Arg7= Likely benign ★★ same residue
MTFMT p.Arg7Cys Uncertain significance ★ ⚠ same residue
MTFMT c.722-2A>G Likely pathogenic ★★ same condition
MTFMT p.Arg128Ter Pathogenic/Likely pathogenic ★★ same condition
MTFMT p.Arg332Ter Pathogenic ★★ same condition
MTFMT p.Ser125Leu Pathogenic/Likely pathogenic ★★ same condition
MTFMT p.Ser209Leu Pathogenic ★★ ⚠ same condition
MTFMT p.Gln355Glu 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/mtfmt-p-arg7gly (accessed [today's date]).

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