Is ASCC1 p.Phe127fs (c.380_381del) pathogenic?

ASCC1 p.Phe127fs (c.380381del) is classified Likely pathogenic in ASCC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). Associated with spinal muscular atrophy with congenital bone fractures 2.

What condition is associated with ASCC1 p.Phe127fs (c.380_381del)?

ASCC1 p.Phe127fs (c.380_381del) is associated with spinal muscular atrophy with congenital bone fractures 2 (ClinVar).

ASCC1 p.Phe127fs

Q: How is Prenatal-onset spinal muscular atrophy with congenital bone fractures inherited?

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

c.380_381del · VCV3377590

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

spinal muscular atrophy with congenital bone fractures 2

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 5 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -2, phastCons 1

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

Variant & gene context

Gene: ASCC1
Protein: p.Phe127fs
Coding: c.380_381del
MANE Select: NM_001198800
Type: Deletion
Location: chr10:72196919 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 1 PDB
Residue 127: the kh domain

Full ASCC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinal muscular atrophy with congenital bone fractures 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Prenatal-onset spinal muscular atrophy with congenital bone fractures (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

ASCC1 p.Glu155fs Pathogenic ★ same condition
ASCC1 p.Phe127= Likely benign ★ same residue
ASCC1 c.311-2A>G Pathogenic ★★ same condition
ASCC1 c.626+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASCC1 c.871+1G>A Pathogenic/Likely pathogenic ★★ same condition
ASCC1 p.Arg110Ter Pathogenic ★★ same condition
ASCC1 p.Arg117Ter Pathogenic ★★ same condition
ASCC1 p.Arg128Ter 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/ascc1-p-phe127fs (accessed [today's date]).

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