Is COASY p.Arg514Gln (c.1541G>A) pathogenic?

COASY p.Arg514Gln (c.1541G>A) is classified Uncertain significance in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-14). AlphaMissense: ambiguous (0.3865); Very rare (popmax 0.00223%, eas).

How common is COASY p.Arg514Gln (c.1541G>A) in the general population?

COASY p.Arg514Gln (c.1541G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about COASY p.Arg514Gln (c.1541G>A)?

AlphaMissense predicts ambiguous (score 0.3865) — an in-silico prediction, not a clinical call.

COASY p.Arg514Gln

c.1541G>A · rs759078658 · VCV2444702

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3865 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3865	ambiguous
REVEL	0.677	pathogenic-leaning
SaProt	LLR -11.80	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 3,342 bp · p 0.88 · regional, not allelic
Overall
CADD	34.0	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 0.00223% East Asian · 1/44,902 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00118% 19/1,613,892 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,902
Admixed American	0.00167%	60,010
European (non-Finnish)	0.00136%	73,752
African / African-American	0.00133%	74,934

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.Arg514Gln
Coding: c.1541G>A
MANE Select: NM_025233
dbSNP: rs759078658
Type: single nucleotide variant
Location: chr17:42565714 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 514: the dpck domain; a UniProt-annotated variant site (in nbia6; reduced protein abundance); a binding site

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

Similar variants

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
COASY p.Ala311Val Uncertain significance ★★ ⚠ same type
COASY p.Ala395Thr 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-arg514gln (accessed [today's date]).

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