Is RNF168 p.Ser93Cys (c.278C>G) pathogenic?

RNF168 p.Ser93Cys (c.278C>G) is classified Conflicting classifications of pathogenicity in RNF168 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-01-31). AlphaMissense: likely benign (0.0893); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RNF168 p.Ser93Cys (c.278C>G)?

RNF168 p.Ser93Cys (c.278C>G) is associated with Inborn genetic diseases (ClinVar).

How common is RNF168 p.Ser93Cys (c.278C>G) in the general population?

RNF168 p.Ser93Cys (c.278C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about RNF168 p.Ser93Cys (c.278C>G)?

AlphaMissense predicts likely benign (score 0.0893) — an in-silico prediction, not a clinical call.

RNF168 p.Ser93Cys

c.278C>G · rs2473979673 · VCV2479076

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0893 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0893	likely benign
REVEL	0.082	moderately benign-leaning
SaProt	LLR -8.43	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 0.8, phastCons 0.95
Regional constraint	o/e 1.06	unconstrained · MANE · 31 kb · p 0.1 · regional, not allelic
Overall
CADD	13.78	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,976 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,822 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.Ser93Cys
Coding: c.278C>G
MANE Select: NM_152617
dbSNP: rs2473979673
Type: single nucleotide variant
Location: chr3:196502896 (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 93: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

RNF168 p.Ser93= Likely benign ★ same residue
RNF168 p.Ala141Val Uncertain significance ★★ ⚠ same condition
RNF168 p.Ala7Ser Uncertain significance ★★ ⚠ same condition
RNF168 p.Arg131Gln Uncertain significance ★★ ⚠ same condition
RNF168 p.Arg132Trp Uncertain significance ★★ ⚠ same condition
RNF168 p.Arg148Ser Uncertain significance ★★ ⚠ same condition
RNF168 p.Arg407Gly Uncertain significance ★★ ⚠ same condition
RNF168 p.Arg466Gln 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/rnf168-p-ser93cys (accessed [today's date]).

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