Is RNF168 p.Cys378fs (c.1130dup) pathogenic?

RNF168 p.Cys378fs (c.1130dup) is classified Pathogenic in RNF168 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). Absent from gnomAD.

How common is RNF168 p.Cys378fs (c.1130dup) in the general population?

RNF168 p.Cys378fs (c.1130dup) is absent from gnomAD (gnomAD).

RNF168 p.Cys378fs

c.1130dup · rs2108644029 · VCV1502151

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (6 of 6) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -3.8, phastCons 0.001

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: RNF168
Protein: p.Cys378fs
Coding: c.1130dup
MANE Select: NM_152617
dbSNP: rs2108644029
Type: Duplication
Location: chr3:196472404 (GRCh38)
Gene constraint: LOEUF 1.406 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.97 · 39 PDB

Full RNF168 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RNF168 p.Cys378= Likely benign ★★ same residue
RNF168 p.Cys378Arg Benign/Likely benign ★★ same residue
RNF168 p.Asn221fs Pathogenic ★ same type
RNF168 p.Cys326fs Pathogenic ★ same type
RNF168 p.Asn532delinsSerTer Uncertain significance ★ same type
RNF168 c.302-19_302-15dup Likely benign ★ same type
RNF168 p.Ala133fs 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/rnf168-p-cys378fs (accessed [today's date]).

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