Is MTFMT p.Arg128Ter (c.382C>T) pathogenic?

MTFMT p.Arg128Ter (c.382C>T) is classified Pathogenic/Likely pathogenic in MTFMT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-11). Very rare (popmax 0.0022%, sas); Associated with combined oxidative phosphorylation defect type 15.

What condition is associated with MTFMT p.Arg128Ter (c.382C>T)?

MTFMT p.Arg128Ter (c.382C>T) is associated with combined oxidative phosphorylation defect type 15, mitochondrial complex I deficiency, nuclear type 27 (ClinVar).

How common is MTFMT p.Arg128Ter (c.382C>T) in the general population?

MTFMT p.Arg128Ter (c.382C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

MTFMT p.Arg128Ter

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.382C>T · rs397514613 · VCV39828

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

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 2 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 9.7	GERP 1.4, phastCons 1
Overall
CADD	39.0	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 0.0022% South Asian · 2/91,032 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000992% 16/1,613,660 alleles · very rare exomes 15/1,461,626 · genomes 1/152,034 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,516
European (non-Finnish)	0.00119%	84,275

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.Arg128Ter
Coding: c.382C>T
MANE Select: NM_139242
dbSNP: rs397514613
Type: single nucleotide variant
Location: chr15:65026868 (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

Also linked: mitochondrial complex I deficiency, nuclear type 27

For Combined oxidative phosphorylation defect type 15 (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MTFMT p.Arg128Gln Uncertain significance ★ ⚠ same residue
MTFMT c.722-2A>G 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
MTFMT p.Arg266Cys Benign ★★ 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-arg128ter (accessed [today's date]).

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