Is COA8 p.Ser43= (c.129A>C) pathogenic?

COA8 p.Ser43= (c.129A>C) is classified Likely benign in COA8 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-01). Ultra-rare (popmax 0.048%, afr); Associated with mitochondrial complex IV deficiency, nuclear type 17.

What condition is associated with COA8 p.Ser43= (c.129A>C)?

COA8 p.Ser43= (c.129A>C) is associated with mitochondrial complex IV deficiency, nuclear type 17 (ClinVar).

How common is COA8 p.Ser43= (c.129A>C) in the general population?

COA8 p.Ser43= (c.129A>C) is ultra-rare (popmax 0.048%, afr) (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.

COA8 p.Ser43=

c.129A>C · rs143925033 · VCV1681861

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.048%, afr)

Conditions

mitochondrial complex IV deficiency, nuclear type 17

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 -0.32	GERP 1.5
Overall
CADD	1.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.048% African / African-American · 36/75,046 alleles

Filtering AF 0.0356% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.00316% 51/1,613,740 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.048%	2,085
Middle Eastern	0.0165%	6,062
Admixed American	0.00667%	14,995
Remaining individualsnot grpmax-eligible	0.0048%	20,827
European (non-Finnish)	0.000593%	168,535

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: COA8
Protein: p.Ser43=
Coding: c.129A>C
MANE Select: NM_001370595
dbSNP: rs143925033
Type: single nucleotide variant
Location: chr14:103571628 (GRCh38)
Gene constraint: LOEUF 1.305 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.19

Full COA8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex IV deficiency, nuclear type 17 — 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

COA8 p.Arg66Ter Pathogenic ★★ same condition
COA8 p.Arg34Leu Uncertain significance ★★ ⚠ same condition
COA8 p.Arg66Gln Uncertain significance ★★ ⚠ same condition
COA8 p.Asp36Tyr Uncertain significance ★★ ⚠ same condition
COA8 p.Glu145Lys Uncertain significance ★★ ⚠ same condition
COA8 p.Glu33Lys Uncertain significance ★★ ⚠ same condition
COA8 p.Pro14Ser Uncertain significance ★★ ⚠ same condition
COA8 p.Pro58Thr 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/coa8-p-ser43 (accessed [today's date]).

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