Is RUSC2 p.Ser243Ter (c.722_727dup) pathogenic?

RUSC2 p.Ser243Ter (c.722727dup) is classified Pathogenic in RUSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-12). No gnomAD frequency available for this variant.

How common is RUSC2 p.Ser243Ter (c.722_727dup) in the general population?

RUSC2 p.Ser243Ter (c.722_727dup) is no gnomAD frequency available for this variant (gnomAD).

RUSC2 p.Ser243Ter

c.722_727dup · rs2132552420 · VCV1431109

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 2 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3	GERP -3.6, 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: RUSC2
Protein: p.Ser243Ter
Coding: c.722_727dup
MANE Select: NM_014806
dbSNP: rs2132552420
Type: Duplication
Location: chr9:35547242 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 45.82 · 1 PDB
Residue 243: the 'disordered' region

Full RUSC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RUSC2 p.Ser243Phe Uncertain significance ★ ⚠ same residue
RUSC2 p.Ser243= Likely benign ★ same residue
RUSC2 c.2015-7_2015-5dup Likely benign ★★ same type
RUSC2 p.Ala739fs Pathogenic ★ same type
RUSC2 p.Arg1404delinsLysTer Pathogenic ★ same type
RUSC2 p.Asn1372fs Likely pathogenic ★ same type
RUSC2 p.Gln106fs Pathogenic ★ same type
RUSC2 p.Glu1246fs Pathogenic ★ same type

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/rusc2-p-ser243ter (accessed [today's date]).

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