Is COASY p.Arg339Pro (c.1016G>C) pathogenic?

COASY p.Arg339Pro (c.1016G>C) is classified Uncertain significance in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.8152); Very rare (popmax 0.00267%, afr).

How common is COASY p.Arg339Pro (c.1016G>C) in the general population?

COASY p.Arg339Pro (c.1016G>C) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about COASY p.Arg339Pro (c.1016G>C)?

AlphaMissense predicts likely pathogenic (score 0.8152) — an in-silico prediction, not a clinical call.

COASY p.Arg339Pro

c.1016G>C · rs768013364 · VCV2333987

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8152 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8152	likely pathogenic
REVEL	0.694	pathogenic-leaning
SaProt	LLR -17.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -1.2, phastCons 0.91
Regional constraint	o/e 0.99	unconstrained · MANE · 3,342 bp · p 0.88 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00267% African / African-American · 2/74,894 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000248% 4/1,613,512 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,447
European (non-Finnish)	0.00017%	589,915

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: COASY
Protein: p.Arg339Pro
Coding: c.1016G>C
MANE Select: NM_025233
dbSNP: rs768013364
Type: single nucleotide variant
Location: chr17:42564546 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 339: a UniProt-annotated variant site (in nbia6; reduced protein abundance); the 'phosphopantetheine adenylyltransferase domain' region

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

Similar variants

COASY p.Arg339Gln Uncertain significance ★ ⚠ same residue
COASY p.Arg339Ter Conflicting classifications of pathogenicity ★ same residue
COASY c.1486-3C>G Pathogenic/Likely pathogenic ★★ same type
COASY p.Ala214Val Likely pathogenic ★★ ⚠ same type
COASY p.Arg377Ter Pathogenic/Likely pathogenic ★★ same type
COASY p.Arg499Cys Pathogenic ★★ same type
COASY p.Gln523Ter Pathogenic ★★ same type
COASY p.Ala206Ser 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/coasy-p-arg339pro (accessed [today's date]).

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