Is RNF168 p.His65fs (c.194_198del) pathogenic?

RNF168 p.His65fs (c.194198del) is classified Pathogenic in RNF168 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-03). Absent from gnomAD.

How common is RNF168 p.His65fs (c.194_198del) in the general population?

RNF168 p.His65fs (c.194_198del) is absent from gnomAD (gnomAD).

RNF168 p.His65fs

c.194_198del · rs2108657396 · VCV1436392

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	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.4	GERP 1.8, 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: RNF168
Protein: p.His65fs
Coding: c.194_198del
MANE Select: NM_152617
dbSNP: rs2108657396
Type: Deletion
Location: chr3:196502976 (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 65: 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.Asp431fs Pathogenic ★ same type
RNF168 p.Gln442fs Likely 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-his65fs (accessed [today's date]).

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