Is COX8A p.Pro31= (c.93G>T) pathogenic?

COX8A p.Pro31= (c.93G>T) is classified Likely benign in COX8A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-02). Rare (popmax 0.163%, sas); Associated with mitochondrial complex IV deficiency, nuclear type 15.

What condition is associated with COX8A p.Pro31= (c.93G>T)?

COX8A p.Pro31= (c.93G>T) is associated with mitochondrial complex IV deficiency, nuclear type 15 (ClinVar).

How common is COX8A p.Pro31= (c.93G>T) in the general population?

COX8A p.Pro31= (c.93G>T) is rare (popmax 0.163%, sas) (gnomAD).

How is Isolated cytochrome C oxidase deficiency inherited?

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

COX8A p.Pro31=

c.93G>T · rs528113495 · VCV1571647

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.163%, sas)

Conditions

mitochondrial complex IV deficiency, nuclear type 15

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 6.1	GERP 0.47, phastCons 1
Overall
CADD	9.92	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% South Asian · 147/89,944 alleles

Filtering AF 0.142% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.0123% 198/1,606,990 alleles · rare exomes 190/1,454,614 · genomes 8/152,376 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.163%	612
Middle Eastern	0.133%	753
Remaining individualsnot grpmax-eligible	0.0209%	4,776
Admixed American	0.0034%	29,429
European (non-Finnish)	0.00229%	43,589
African / African-American	0.00133%	74,980

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: COX8A
Protein: p.Pro31=
Coding: c.93G>T
MANE Select: NM_004074
dbSNP: rs528113495
Type: single nucleotide variant
Location: chr11:63974773 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74 · 4 PDB
Residue 31: an α-helix

Full COX8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Isolated cytochrome C oxidase deficiency (Orphanet):

Inheritance: Autosomal recessive, Mitochondrial inheritance

Similar variants

COX8A c.114+17G>A Likely benign ★★ same condition
COX8A p.Ile37= Benign/Likely benign ★★ same condition
COX8A p.Ile58= Benign/Likely benign ★★ same condition
COX8A p.Trp57Cys Uncertain significance ★★ ⚠ same type
COX8A p.Arg23Cys Benign/Likely benign ★★ same type
COX8A p.Leu8= Benign ★★ same type
COX8A p.Glu39Gly Uncertain significance ★ ⚠ same type
COX8A p.Glu39Lys Uncertain significance ★ ⚠ same type

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/cox8a-p-pro31 (accessed [today's date]).

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