Is TMEM70 p.Pro9= (c.27G>T) pathogenic?

TMEM70 p.Pro9= (c.27G>T) is classified Likely benign in TMEM70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-15). No allele count reported in gnomAD v4.1 (AN 1,600,876); Associated with mitochondrial complex V (ATP synthase) deficiency, nuclear type 2.

What condition is associated with TMEM70 p.Pro9= (c.27G>T)?

TMEM70 p.Pro9= (c.27G>T) is associated with mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (ClinVar).

How common is TMEM70 p.Pro9= (c.27G>T) in the general population?

TMEM70 p.Pro9= (c.27G>T) is no allele count reported in gnomAD v4.1 (AN 1,600,876) (gnomAD).

TMEM70 p.Pro9=

Q: How is TMEM70-related mitochondrial encephalo-cardio-myopathy inherited?

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

c.27G>T · rs1260525805 · VCV2697923

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,876)

Conditions

mitochondrial complex V (ATP synthase) deficiency, nuclear type 2

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 0.81	GERP 0.11
Overall
CADD	6.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,876). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TMEM70
Protein: p.Pro9=
Coding: c.27G>T
MANE Select: NM_017866
dbSNP: rs1260525805
Type: single nucleotide variant
Location: chr8:73976308 (GRCh38)
Gene constraint: LOEUF 1.375 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.16

Full TMEM70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For TMEM70-related mitochondrial encephalo-cardio-myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

TMEM70 p.Pro9Leu Uncertain significance ★ ⚠ same residue
TMEM70 p.Pro9Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TMEM70 c.317-2A>G Pathogenic/Likely pathogenic ★★ same condition
TMEM70 p.Arg80Ter Pathogenic ★★ same condition
TMEM70 p.Ala174Thr Uncertain significance ★★ ⚠ same condition
TMEM70 p.Ala205Ser Uncertain significance ★★ ⚠ same condition
TMEM70 p.Arg255Trp Uncertain significance ★★ ⚠ same condition
TMEM70 p.Arg80Gln 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/tmem70-p-pro9 (accessed [today's date]).

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