Is COASY p.Ala383= (c.1149G>A) pathogenic?

COASY p.Ala383= (c.1149G>A) is classified Likely benign in COASY (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). Ultra-rare (popmax 0.0101%, amr); Associated with neurodegeneration with brain iron accumulation 6.

What condition is associated with COASY p.Ala383= (c.1149G>A)?

COASY p.Ala383= (c.1149G>A) is associated with neurodegeneration with brain iron accumulation 6 (ClinVar).

How common is COASY p.Ala383= (c.1149G>A) in the general population?

COASY p.Ala383= (c.1149G>A) is ultra-rare (popmax 0.0101%, 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.Ala383=

c.1149G>A · rs775259112 · VCV512134

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.9	GERP -4.7
Overall
CADD	0.092	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% Admixed American · 5/49,268 alleles

Filtering AF 0.00393% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00265%

Overall 0.0034% 53/1,557,174 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,854
European (non-Finnish)	0.00389%	25,693
Remaining individualsnot grpmax-eligible	0.00334%	29,969
South Asian	0.00123%	80,982

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.Ala383=
Coding: c.1149G>A
MANE Select: NM_025233
dbSNP: rs775259112
Type: single nucleotide variant
Location: chr17:42564810 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 383: the dpck domain; 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

COASY p.Ala383Thr 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-ala383 (accessed [today's date]).

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