Is COASY p.Val196fs (c.586_587del) pathogenic?

COASY p.Val196fs (c.586587del) is classified Likely pathogenic in COASY (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Associated with pontocerebellar hypoplasia, type 12.

What condition is associated with COASY p.Val196fs (c.586_587del)?

COASY p.Val196fs (c.586_587del) is associated with pontocerebellar hypoplasia, type 12 (ClinVar).

COASY p.Val196fs

c.586_587del · VCV3775291

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

pontocerebellar hypoplasia, type 12

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 4.8	GERP 2.5, phastCons 1

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

Variant & gene context

Gene: COASY
Protein: p.Val196fs
Coding: c.586_587del
MANE Select: NM_025233
Type: Deletion
Location: chr17:42563207 (GRCh38)
Gene constraint: LOEUF 0.791 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.51
Residue 196: 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

pontocerebellar hypoplasia, type 12 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COASY c.1238-24_1238-20del Uncertain significance ★ same condition
COASY c.1486-3C>G Pathogenic/Likely pathogenic ★★ same condition
COASY p.Arg377Ter Pathogenic/Likely pathogenic ★★ same condition
COASY p.Ser517fs Pathogenic/Likely pathogenic ★★ same condition
COASY p.Arg543His Uncertain significance ★★ ⚠ same condition
COASY p.Arg555His Uncertain significance ★★ ⚠ same condition
COASY p.His40Tyr Uncertain significance ★★ ⚠ same condition
COASY p.Ser55Tyr Benign ★★ 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-val196fs (accessed [today's date]).

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