Is MTO1 p.Val231= (c.693G>T) pathogenic?

MTO1 p.Val231= (c.693G>T) is classified Likely benign in MTO1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-07). Very rare (popmax 0.00373%, nfe); Associated with mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency.

How common is MTO1 p.Val231= (c.693G>T) in the general population?

MTO1 p.Val231= (c.693G>T) is very rare (popmax 0.00373%, nfe) (gnomAD).

MTO1 p.Val231=

Q: What condition is associated with MTO1 p.Val231= (c.693G>T)?

MTO1 p.Val231= (c.693G>T) is associated with mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (ClinVar).

Q: How is Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency inherited?

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

c.693G>T · rs558715877 · VCV700540

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00373%, nfe)

Conditions

mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -4.2
Overall
CADD	3.992	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00373% European (non-Finnish) · 44/1,180,024 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00315% 46/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00373%	26,819
Remaining individualsnot grpmax-eligible	0.0032%	31,251

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: MTO1
Protein: p.Val231=
Coding: c.693G>T
MANE Select: NM_012123
dbSNP: rs558715877
Type: single nucleotide variant
Location: chr6:73473522 (GRCh38)
Gene constraint: LOEUF 0.82 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.95

Full MTO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mitochondrial hypertrophic cardiomyopathy with lactic acidosis due to MTO1 deficiency (Orphanet):

Inheritance: Unknown
Onset: Infancy, Neonatal

Similar variants

MTO1 p.Val231Leu Uncertain significance ★★ ⚠ same residue
MTO1 c.417+2T>C Likely pathogenic ★★ same condition
MTO1 p.Ala428Thr Pathogenic/Likely pathogenic ★★ same condition
MTO1 p.Arg442Ter Pathogenic/Likely pathogenic ★★ same condition
MTO1 p.Arg464Cys Likely pathogenic ★★ same condition
MTO1 p.Arg469Ter Pathogenic/Likely pathogenic ★★ same condition
MTO1 p.Arg484Trp Pathogenic/Likely pathogenic ★★ same condition
MTO1 p.Arg488Ter Pathogenic ★★ 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/mto1-p-val231 (accessed [today's date]).

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