Is MTFMT p.Phe367fs (c.1100_1101del) pathogenic?

MTFMT p.Phe367fs (c.11001101del) is classified Pathogenic/Likely pathogenic in MTFMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-04-23). Very rare (popmax 0.00017%, nfe); Associated with mitochondrial oxidative phosphorylation disorder.

What condition is associated with MTFMT p.Phe367fs (c.1100_1101del)?

MTFMT p.Phe367fs (c.1100_1101del) is associated with mitochondrial oxidative phosphorylation disorder (ClinVar).

How common is MTFMT p.Phe367fs (c.1100_1101del) in the general population?

MTFMT p.Phe367fs (c.1100_1101del) is very rare (popmax 0.00017%, nfe) (gnomAD).

MTFMT p.Phe367fs

c.1100_1101del · rs754222633 · VCV506018

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

mitochondrial oxidative phosphorylation disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (9 of 9) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 0.73, phastCons 1
Overall
CADD	33.0	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 0.00017% European (non-Finnish) · 2/1,179,598 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,140 alleles · very rare exomes 0/1,461,046 · genomes 2/152,094 · joint denominator

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.Phe367fs
Coding: c.1100_1101del
MANE Select: NM_139242
dbSNP: rs754222633
Type: Deletion
Location: chr15:65003131 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 367: a UniProt-annotated variant site (in mc1dn27)

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

Disease context

mitochondrial oxidative phosphorylation disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MTFMT p.Arg49fs Pathogenic/Likely pathogenic ★★ same type
MTFMT p.Glu74fs Pathogenic ★★ same type
MTFMT p.Pro373fs Likely pathogenic ★★ same type
MTFMT c.892+17del Benign/Likely benign ★★ same type
MTFMT c.976-20del Likely benign ★★ same type
MTFMT c.209+2_209+14del Likely pathogenic ★ same type
MTFMT p.Arg231fs Pathogenic ★ same type
MTFMT p.Leu211fs Pathogenic ★ same type

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-phe367fs (accessed [today's date]).

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