Is COASY p.Arg300Cys (c.898C>T) pathogenic?

COASY p.Arg300Cys (c.898C>T) is classified Uncertain significance in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely benign (0.1064); Ultra-rare (popmax 0.0164%, mid).

How common is COASY p.Arg300Cys (c.898C>T) in the general population?

COASY p.Arg300Cys (c.898C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about COASY p.Arg300Cys (c.898C>T)?

AlphaMissense predicts likely benign (score 0.1064) — an in-silico prediction, not a clinical call.

COASY p.Arg300Cys

c.898C>T · rs1264878421 · VCV2394546

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1064 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1064	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -11.29	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 3,342 bp · p 0.88 · regional, not allelic
Overall
CADD	28.2	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000929% 15/1,613,884 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,241
East Asian	0.00223%	44,890
South Asian	0.0022%	45,534
Admixed American	0.00167%	59,976
African / African-American	0.00134%	74,900
European (non-Finnish)	0.000593%	168,570

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.Arg300Cys
Coding: c.898C>T
MANE Select: NM_025233
dbSNP: rs1264878421
Type: single nucleotide variant
Location: chr17:42564158 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 300: 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 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-arg300cys (accessed [today's date]).

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