Is MTFMT p.Arg31Ter (c.91C>T) pathogenic?

MTFMT p.Arg31Ter (c.91C>T) is classified Pathogenic in MTFMT (ClinVar, Single submitter, 1 submitter; last evaluated 2017-11-08). Ultra-rare (popmax 0.0181%, mid); Associated with combined oxidative phosphorylation defect type 15.

What condition is associated with MTFMT p.Arg31Ter (c.91C>T)?

MTFMT p.Arg31Ter (c.91C>T) is associated with combined oxidative phosphorylation defect type 15 (ClinVar).

How common is MTFMT p.Arg31Ter (c.91C>T) in the general population?

MTFMT p.Arg31Ter (c.91C>T) is ultra-rare (popmax 0.0181%, mid) (gnomAD).

MTFMT p.Arg31Ter

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.91C>T · rs1555404423 · VCV488549

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0181%, mid)

Conditions

combined oxidative phosphorylation defect type 15

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -2.4
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0181% Middle Eastern · 1/5,526 alleles

Overall 0.000131% 2/1,528,198 alleles · ultra-rare exomes 2/1,375,920 · genomes 0/152,278 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0181%	5,526
European (non-Finnish)	8.77e-05%	1,139,622

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.Arg31Ter
Coding: c.91C>T
MANE Select: NM_139242
dbSNP: rs1555404423
Type: single nucleotide variant
Location: chr15:65029523 (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.Arg31Pro 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.Arg7Gly Uncertain significance ★★ ⚠ 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-arg31ter (accessed [today's date]).

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