Is COASY p.Asp201Ter (c.600dup) pathogenic?

COASY p.Asp201Ter (c.600dup) is classified Pathogenic/Likely pathogenic in COASY (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-01). Very rare (popmax 0.00167%, amr); Associated with neurodegeneration with brain iron accumulation 6.

What condition is associated with COASY p.Asp201Ter (c.600dup)?

COASY p.Asp201Ter (c.600dup) is associated with neurodegeneration with brain iron accumulation 6 (ClinVar).

How common is COASY p.Asp201Ter (c.600dup) in the general population?

COASY p.Asp201Ter (c.600dup) is very rare (popmax 0.00167%, amr) (gnomAD).

How is COASY protein-associated neurodegeneration inherited?

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

COASY p.Asp201Ter

c.600dup · VCV4704971

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

neurodegeneration with brain iron accumulation 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -3.8	GERP -5

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,030 alleles

Overall 6.84e-05% 1/1,461,316 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: COASY
Protein: p.Asp201Ter
Coding: c.600dup
MANE Select: NM_025233
Type: Duplication
Location: chr17:42563219 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 201: 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

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

COASY p.Asp201Gly Uncertain significance ★ ⚠ same residue
COASY p.Tyr141Ter Pathogenic ★ same condition
COASY p.Tyr38fs Likely pathogenic ★ same condition
COASY p.Ala19fs Conflicting classifications of pathogenicity ★ same condition
COASY c.1485+19dup Benign ★ same condition
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

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-asp201ter (accessed [today's date]).

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