Is COASY p.Glu63= (c.189G>A) pathogenic?

COASY p.Glu63= (c.189G>A) is classified Likely benign in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-04). Very rare (popmax 0.00669%, eas); Associated with neurodegeneration with brain iron accumulation 6.

What condition is associated with COASY p.Glu63= (c.189G>A)?

COASY p.Glu63= (c.189G>A) is associated with neurodegeneration with brain iron accumulation 6 (ClinVar).

How common is COASY p.Glu63= (c.189G>A) in the general population?

COASY p.Glu63= (c.189G>A) is very rare (popmax 0.00669%, eas) (gnomAD).

How is COASY protein-associated neurodegeneration inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

COASY p.Glu63=

c.189G>A · VCV4694044

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Conditions

neurodegeneration with brain iron accumulation 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -0.97, phastCons 1
Overall
CADD	10.09	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,848 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.000548% 8/1,460,420 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,949
Remaining individualsnot grpmax-eligible	0.0016%	62,460
European (non-Finnish)	0.000339%	294,830

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.Glu63=
Coding: c.189G>A
MANE Select: NM_025233
Type: single nucleotide variant
Location: chr17:42562811 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 63: a UniProt-annotated variant site (in nbia6; reduced protein abundance)

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

Disease context

neurodegeneration with brain iron accumulation 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For COASY protein-associated neurodegeneration (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

PPAT p.Ser63Leu Uncertain significance ★ ⚠ same residue
COASY c.1486-3C>G Pathogenic/Likely pathogenic ★★ same condition
COASY p.Ala214Val Likely pathogenic ★★ ⚠ same condition
COASY p.Arg377Ter Pathogenic/Likely pathogenic ★★ same condition
COASY p.Arg499Cys Pathogenic ★★ same condition
COASY p.Gln523Ter Pathogenic ★★ same condition
COASY p.Ala206Ser Uncertain significance ★★ ⚠ same condition
COASY p.Ala311Val 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/coasy-p-glu63 (accessed [today's date]).

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