Is COASY c.1237+7A>G pathogenic?

COASY c.1237+7A>G is classified Likely benign in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). Very rare (popmax 8.48e-05%, nfe); Associated with neurodegeneration with brain iron accumulation 6.

What condition is associated with COASY c.1237+7A>G?

COASY c.1237+7A>G is associated with neurodegeneration with brain iron accumulation 6 (ClinVar).

How common is COASY c.1237+7A>G in the general population?

COASY c.1237+7A>G is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is COASY protein-associated neurodegeneration inherited?

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

COASY c.1237+7A>G

rs2510682664 · VCV2794461

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

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
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.58	GERP -4.7
Non-coding constraint	Z 2.72	1 kb window · o/e 0.82 · regional · uncalibrated
Overall
CADD	4.001	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,604 alleles

Overall 6.84e-05% 1/1,461,224 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
Coding: c.1237+7A>G
MANE Select: NM_025233
dbSNP: rs2510682664
Type: single nucleotide variant
Location: chr17:42564905 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51

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 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
COASY p.Ala395Thr 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-c-1237-plus-7a-g (accessed [today's date]).

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