Is COA8 p.Pro73Ala (c.217C>G) pathogenic?

COA8 p.Pro73Ala (c.217C>G) is classified Uncertain significance in COA8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1584); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with COA8 p.Pro73Ala (c.217C>G)?

COA8 p.Pro73Ala (c.217C>G) is associated with Inborn genetic diseases (ClinVar).

How common is COA8 p.Pro73Ala (c.217C>G) in the general population?

COA8 p.Pro73Ala (c.217C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about COA8 p.Pro73Ala (c.217C>G)?

AlphaMissense predicts likely benign (score 0.1584) — an in-silico prediction, not a clinical call.

COA8 p.Pro73Ala

c.217C>G · rs1273644581 · VCV2492989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1584	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -13.71	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	Δ0.27	acceptor gain · deltas
Pangolin	Δ0.20	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 5.7	GERP 0.77, phastCons 1
Regional constraint	o/e 1.16	unconstrained · MANE · 27 kb · p 0.018 · regional, not allelic
Overall
CADD	23.1	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 P86A vs ClinVar P73A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,082 alleles

Overall 6.84e-05% 1/1,461,746 alleles · very rare

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.Pro73Ala
Coding: c.217C>G
MANE Select: NM_001370595
dbSNP: rs1273644581
Type: single nucleotide variant
Location: chr14:103571716 (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

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

Similar variants

COA8 p.Pro73His Uncertain significance ★ ⚠ same residue
COA8 c.-32C>G Uncertain significance ★★ ⚠ same condition
COA8 p.Ala140Val Uncertain significance ★★ ⚠ same condition
COA8 p.Ala27Val Uncertain significance ★★ ⚠ same condition
COA8 p.Arg164Cys Uncertain significance ★★ ⚠ same condition
COA8 p.Asn135Ser Uncertain significance ★★ ⚠ same condition
COA8 p.Asn165Ser Uncertain significance ★★ ⚠ same condition
COA8 p.Gln88Arg 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-pro73ala (accessed [today's date]).

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