Is ASCC1 p.Arg110Ter (c.328C>T) pathogenic?

ASCC1 p.Arg110Ter (c.328C>T) is classified Pathogenic in ASCC1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-06-07). Very rare (popmax 0.00333%, amr); Associated with spinal muscular atrophy with congenital bone fractures 2.

How common is ASCC1 p.Arg110Ter (c.328C>T) in the general population?

ASCC1 p.Arg110Ter (c.328C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

ASCC1 p.Arg110Ter

Q: What condition is associated with ASCC1 p.Arg110Ter (c.328C>T)?

ASCC1 p.Arg110Ter (c.328C>T) is associated with spinal muscular atrophy with congenital bone fractures 2, centronuclear myopathy (ClinVar).

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.328C>T · rs866050664 · VCV801335

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 10
REVEL	0.337	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.8, phastCons 1
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,998 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.00103% 15/1,461,406 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,833
Admixed Americangrpmax	0.00333%	29,999
African / African-American	0.00267%	37,506
East Asian	0.00223%	44,872
European (non-Finnish)	0.000593%	168,571

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ASCC1
Protein: p.Arg110Ter
Coding: c.328C>T
MANE Select: NM_001198800
dbSNP: rs866050664
Type: single nucleotide variant
Location: chr10:72196972 (GRCh38)
Gene constraint: LOEUF 1.002 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.70 · 1 PDB
Residue 110: 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

Also linked: centronuclear myopathy

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.Arg110Gln Uncertain significance ★ ⚠ 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.Arg117Ter Pathogenic ★★ same condition
ASCC1 p.Arg128Ter Pathogenic ★★ same condition
ASCC1 p.Gln195Ter Pathogenic/Likely pathogenic ★★ same condition
ASCC1 p.Gln262Ter 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-arg110ter (accessed [today's date]).

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