Is RUSC2 p.Arg925Ter (c.2773C>T) pathogenic?

RUSC2 p.Arg925Ter (c.2773C>T) is classified Likely pathogenic in RUSC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-12). Very rare (popmax 0.00167%, amr); Associated with intellectual disability, autosomal recessive 61.

What condition is associated with RUSC2 p.Arg925Ter (c.2773C>T)?

RUSC2 p.Arg925Ter (c.2773C>T) is associated with intellectual disability, autosomal recessive 61 (ClinVar).

How common is RUSC2 p.Arg925Ter (c.2773C>T) in the general population?

RUSC2 p.Arg925Ter (c.2773C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

RUSC2 p.Arg925Ter

c.2773C>T · rs765514069 · VCV931076

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

intellectual disability, autosomal recessive 61

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 4 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Overall
CADD	38.0	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 0.00167% Admixed American · 1/60,022 alleles

Overall 6.2e-05% 1/1,614,182 alleles · very rare exomes 1/1,461,892 · genomes 0/152,290 · joint denominator

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: RUSC2
Protein: p.Arg925Ter
Coding: c.2773C>T
MANE Select: NM_014806
dbSNP: rs765514069
Type: single nucleotide variant
Location: chr9:35556068 (GRCh38)
Gene constraint: LOEUF 0.383 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 45.82 · 1 PDB
Residue 925: a UniProt-annotated variant site (in mrt61; uncertain significance)

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

Disease context

intellectual disability, autosomal recessive 61 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RUSC2 p.Arg925Gln Uncertain significance ★★ ⚠ same residue
RUSC2 p.Arg1393Ter Pathogenic/Likely pathogenic ★★ same condition
RUSC2 p.Ala745Thr Uncertain significance ★★ ⚠ same condition
RUSC2 p.Arg1015Gln Uncertain significance ★★ same condition
RUSC2 p.Arg1186Gln Uncertain significance ★★ ⚠ same condition
RUSC2 p.Arg1360Gln Uncertain significance ★★ ⚠ same condition
RUSC2 p.Arg1360Trp Uncertain significance ★★ ⚠ same condition
RUSC2 p.Arg510Cys 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/rusc2-p-arg925ter (accessed [today's date]).

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