Is MTFMT p.Arg332Ter (c.994C>T) pathogenic?

MTFMT p.Arg332Ter (c.994C>T) is classified Pathogenic in MTFMT (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-04-14). Very rare (popmax 0.00992%, nfe); Associated with mitochondrial complex I deficiency, nuclear type 27.

What condition is associated with MTFMT p.Arg332Ter (c.994C>T)?

MTFMT p.Arg332Ter (c.994C>T) is associated with mitochondrial complex I deficiency, nuclear type 27, combined oxidative phosphorylation defect type 15 (ClinVar).

How common is MTFMT p.Arg332Ter (c.994C>T) in the general population?

MTFMT p.Arg332Ter (c.994C>T) is very rare (popmax 0.00992%, nfe) (gnomAD).

MTFMT p.Arg332Ter

c.994C>T · rs200286768 · VCV39830

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00992%, nfe)

Conditions

mitochondrial complex I deficiency, nuclear type 27

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	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.7, phastCons 1
Overall
CADD	38.0	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 0.00992% European (non-Finnish) · 117/1,179,184 alleles

Filtering AF 0.00843% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00788%

Overall 0.00794% 128/1,612,598 alleles · very rare exomes 113/1,460,536 · genomes 15/152,062 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00992%	10,078
Remaining individualsnot grpmax-eligible	0.00801%	12,480
Admixed American	0.00334%	29,935
African / African-American	0.00267%	37,426
Finnishnot grpmax-eligible	0.00156%	63,916
South Asian	0.0011%	90,948

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.Arg332Ter
Coding: c.994C>T
MANE Select: NM_139242
dbSNP: rs200286768
Type: single nucleotide variant
Location: chr15:65003238 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.08
Residue 332: a UniProt-annotated variant site (in mc1dn27)

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

Disease context

mitochondrial complex I deficiency, nuclear type 27 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: combined oxidative phosphorylation defect type 15

Similar variants

MTFMT c.722-2A>G Likely pathogenic ★★ same condition
MTFMT p.Arg128Ter Pathogenic/Likely 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
MTFMT p.Phe58Ile 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-arg332ter (accessed [today's date]).

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