Is COASY p.Pro128fs (c.383del) pathogenic?

COASY p.Pro128fs (c.383del) is classified Pathogenic in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-26). Absent from gnomAD; Associated with neurodegeneration with brain iron accumulation 6.

What condition is associated with COASY p.Pro128fs (c.383del)?

COASY p.Pro128fs (c.383del) is associated with neurodegeneration with brain iron accumulation 6 (ClinVar).

How common is COASY p.Pro128fs (c.383del) in the general population?

COASY p.Pro128fs (c.383del) is absent from gnomAD (gnomAD).

How is COASY protein-associated neurodegeneration inherited?

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

COASY p.Pro128fs

c.383del · rs2510677991 · VCV1899292

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	frameshift	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 11	GERP 2.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COASY
Protein: p.Pro128fs
Coding: c.383del
MANE Select: NM_025233
dbSNP: rs2510677991
Type: Deletion
Location: chr17:42563003 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 128: 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.Pro128Leu Uncertain significance ★ ⚠ same residue
COASY p.Pro128Thr Uncertain significance ★ ⚠ same residue
COASY p.Pro128= Likely benign ★ same residue
COASY p.Gly159del Uncertain significance ★★ same condition
COASY c.1302+19del Likely benign ★★ same condition
COASY p.Ala30_Arg31insTer Likely pathogenic ★ same condition
COASY p.Gly182fs Pathogenic ★ same condition
COASY p.Phe62fs 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-pro128fs (accessed [today's date]).

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