Is COX8A p.Arg23Cys (c.67C>T) pathogenic?

COX8A p.Arg23Cys (c.67C>T) is classified Benign/Likely benign in COX8A (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-07). AlphaMissense: likely benign (0.2768); Rare (popmax 0.864%, afr).

How common is COX8A p.Arg23Cys (c.67C>T) in the general population?

COX8A p.Arg23Cys (c.67C>T) is rare (popmax 0.864%, afr) (gnomAD).

What do computational predictors say about COX8A p.Arg23Cys (c.67C>T)?

AlphaMissense predicts likely benign (score 0.2768) — an in-silico prediction, not a clinical call.

COX8A p.Arg23Cys

c.67C>T · rs144339685 · VCV771443

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.2768 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.864%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2768	likely benign
REVEL	0.174	moderately benign-leaning
SaProt	LLR -6.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.56, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 1,636 bp · p 0.063 · regional, not allelic
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.864% African / African-American · 648/74,958 alleles

Filtering AF 0.809% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.787%

Overall 0.0601% 967/1,608,092 alleles · rare exomes 600/1,455,744 · genomes 367/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.864%	116
Middle Eastern	0.348%	287
Admixed American	0.156%	643
Remaining individualsnot grpmax-eligible	0.122%	817
European (non-Finnish)	0.0106%	9,421
South Asian	0.00555%	18,023

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.Arg23Cys
Coding: c.67C>T
MANE Select: NM_004074
dbSNP: rs144339685
Type: single nucleotide variant
Location: chr11:63974747 (GRCh38)
Gene constraint: LOEUF 1.922 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.74 · 4 PDB

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

Similar variants

COX8A p.Arg23= Likely benign ★ same residue
COX8A p.Trp57Cys Uncertain significance ★★ ⚠ same type
COX8A c.114+17G>A Likely benign ★★ same type
COX8A p.Ile37= Benign/Likely benign ★★ same type
COX8A p.Ile58= Benign/Likely benign ★★ same type
COX8A p.Leu8= Benign ★★ same type
COX8A p.Pro31= Likely benign ★★ same type
COX8A p.Glu39Gly 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-arg23cys (accessed [today's date]).

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