Is RNF168 p.Asp431fs (c.1290_1293del) pathogenic?

RNF168 p.Asp431fs (c.12901293del) is classified Pathogenic in RNF168 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). Very rare (popmax 0.000254%, nfe).

How common is RNF168 p.Asp431fs (c.1290_1293del) in the general population?

RNF168 p.Asp431fs (c.1290_1293del) is very rare (popmax 0.000254%, nfe) (gnomAD).

RNF168 p.Asp431fs

c.1290_1293del · VCV3724991

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

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 3	GERP -0.55, phastCons 1
Overall
CADD	29.7	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 0.000254% European (non-Finnish) · 3/1,179,960 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,924 alleles · very rare

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: RNF168
Protein: p.Asp431fs
Coding: c.1290_1293del
MANE Select: NM_152617
Type: Deletion
Location: chr3:196472242 (GRCh38)
Gene constraint: LOEUF 1.406 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.97 · 39 PDB
Residue 431: an α-helix

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

Similar variants

RNF168 p.Arg220fs Pathogenic/Likely pathogenic ★★ same type
RNF168 p.Cys50fs Pathogenic ★★ same type
RNF168 p.Ala161fs Pathogenic ★ same type
RNF168 p.Ala405fs Pathogenic ★ same type
RNF168 p.Asn187fs Pathogenic ★ same type
RNF168 p.Asn488fs Likely pathogenic ★ same type
RNF168 p.Gln442fs Likely pathogenic ★ same type
RNF168 p.Glu170fs 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-asp431fs (accessed [today's date]).

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