Is COQ9 p.Pro80Ala (c.238C>G) pathogenic?

COQ9 p.Pro80Ala (c.238C>G) is classified Uncertain significance in COQ9 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-25). AlphaMissense: likely benign (0.0658); Very rare (popmax 0.004%, afr); Associated with Inborn genetic diseases.

What condition is associated with COQ9 p.Pro80Ala (c.238C>G)?

COQ9 p.Pro80Ala (c.238C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COQ9 p.Pro80Ala (c.238C>G) in the general population?

COQ9 p.Pro80Ala (c.238C>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about COQ9 p.Pro80Ala (c.238C>G)?

AlphaMissense predicts likely benign (score 0.0658) — an in-silico prediction, not a clinical call.

COQ9 p.Pro80Ala

c.238C>G · rs1366599130 · VCV1926430

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0658 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0658	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -6.20	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 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 13 kb · p 0.67 · regional, not allelic
Overall
CADD	19.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,032 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000342% 5/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,011
South Asian	0.0022%	45,541

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: COQ9
Protein: p.Pro80Ala
Coding: c.238C>G
MANE Select: NM_020312
dbSNP: rs1366599130
Type: single nucleotide variant
Location: chr16:57451204 (GRCh38)
Gene constraint: LOEUF 1.035 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.16 · 5 PDB
Residue 80: the 'disordered' region

Full COQ9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COQ9 p.Pro80= Benign/Likely benign ★★ same residue
COQ9 c.242+5G>A Uncertain significance ★★ same condition
COQ9 p.Ala120Val Uncertain significance ★★ ⚠ same condition
COQ9 p.Ala122Thr Uncertain significance ★★ ⚠ same condition
COQ9 p.Ala13Gly Uncertain significance ★★ ⚠ same condition
COQ9 p.Ala304Val Uncertain significance ★★ ⚠ same condition
COQ9 p.Ala4Val Uncertain significance ★★ ⚠ same condition
COQ9 p.Ala5Gly 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/coq9-p-pro80ala (accessed [today's date]).

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