Is COA8 p.Pro14Arg (c.41C>G) pathogenic?

COA8 p.Pro14Arg (c.41C>G) is classified Benign/Likely benign in COA8 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0624); Low-frequency (popmax 1.85%, afr).

How common is COA8 p.Pro14Arg (c.41C>G) in the general population?

COA8 p.Pro14Arg (c.41C>G) is low-frequency (popmax 1.85%, afr) (gnomAD).

What do computational predictors say about COA8 p.Pro14Arg (c.41C>G)?

AlphaMissense predicts likely benign (score 0.0624) — an in-silico prediction, not a clinical call.

COA8 p.Pro14Arg

c.41C>G · rs74917403 · VCV382991

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0624 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.85%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0624	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.82	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 -2.5	GERP -2
Regional constraint	o/e 1.16	unconstrained · MANE · 27 kb · p 0.018 · regional, not allelic
Overall
CADD	0.216	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P27R vs ClinVar P14R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.85% African / African-American · 1,357/73,452 alleles

Filtering AF 1.77% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.73%

Overall 0.102% 1,578/1,543,338 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.85%	54
Middle Eastern	0.123%	815
Remaining individualsnot grpmax-eligible	0.11%	911
South Asian	0.0942%	1,062
Admixed American	0.0749%	1,336
European (non-Finnish)	0.00252%	39,654

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.Pro14Arg
Coding: c.41C>G
MANE Select: NM_001370595
dbSNP: rs74917403
Type: single nucleotide variant
Location: chr14:103563042 (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

Similar variants

COA8 p.Pro14His Uncertain significance ★★ ⚠ same residue
COA8 p.Pro14Ser Uncertain significance ★★ ⚠ same residue
COA8 p.Pro14Ala Benign/Likely benign ★★ same residue
COA8 p.Pro14Thr Likely benign ★★ same residue
COA8 p.Pro14Leu Uncertain significance ★ ⚠ same residue
COA8 p.Arg66Ter Pathogenic ★★ same type
COA8 c.-32C>G Uncertain significance ★★ ⚠ same type
COA8 p.Ala140Val 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/coa8-p-pro14arg (accessed [today's date]).

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