Is TMEM70 p.Ser8Pro (c.22_23delinsCC) pathogenic?

TMEM70 p.Ser8Pro (c.2223delinsCC) is classified Uncertain significance in TMEM70 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-05). Absent from gnomAD; Associated with mitochondrial complex V (ATP synthase) deficiency, nuclear type 2.

What condition is associated with TMEM70 p.Ser8Pro (c.22_23delinsCC)?

TMEM70 p.Ser8Pro (c.22_23delinsCC) is associated with mitochondrial complex V (ATP synthase) deficiency, nuclear type 2 (ClinVar).

How common is TMEM70 p.Ser8Pro (c.22_23delinsCC) in the general population?

TMEM70 p.Ser8Pro (c.22_23delinsCC) is absent from gnomAD (gnomAD).

TMEM70 p.Ser8Pro

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.22_23delinsCC · rs2536389330 · VCV2123547

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 · substitutions only
Constraint at this position
Conservation	phyloP 0.024	GERP -4
Regional constraint	o/e 1.04	unconstrained · MANE · 5,336 bp · p 0.5 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser8Pro
Coding: c.22_23delinsCC
MANE Select: NM_017866
dbSNP: rs2536389330
Type: Indel
Location: chr8:73976303 (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.Ser8Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
TMEM70 p.Pro123Leu Uncertain significance ★ same condition
TMEM70 c.317-2A>G Pathogenic/Likely pathogenic ★★ same condition
TMEM70 p.Ala11fs Pathogenic/Likely pathogenic ★★ same condition
TMEM70 p.Ala34fs Pathogenic/Likely pathogenic ★★ same condition
TMEM70 p.Arg80Ter Pathogenic ★★ same condition
TMEM70 p.Gly149fs Pathogenic/Likely pathogenic ★★ same condition
TMEM70 p.Ser40fs Pathogenic/Likely 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/tmem70-p-ser8pro (accessed [today's date]).

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