Is RNF168 p.Gln245Pro (c.734A>C) pathogenic?

RNF168 p.Gln245Pro (c.734A>C) is classified Uncertain significance in RNF168 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-20). AlphaMissense: likely benign (0.0761); Very rare (popmax 0.00134%, afr); Associated with Inborn genetic diseases.

What condition is associated with RNF168 p.Gln245Pro (c.734A>C)?

RNF168 p.Gln245Pro (c.734A>C) is associated with Inborn genetic diseases (ClinVar).

How common is RNF168 p.Gln245Pro (c.734A>C) in the general population?

RNF168 p.Gln245Pro (c.734A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about RNF168 p.Gln245Pro (c.734A>C)?

AlphaMissense predicts likely benign (score 0.0761) — an in-silico prediction, not a clinical call.

RNF168 p.Gln245Pro

c.734A>C · VCV3789652

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0761 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0761	likely benign
REVEL	0.131	moderately benign-leaning
SaProt	LLR -5.59	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 -0.038	GERP -2.3
Regional constraint	o/e 1.06	unconstrained · MANE · 31 kb · p 0.1 · regional, not allelic
Overall
CADD	13.16	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,854 alleles

Filtering AF 0.000544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00043%

Overall 0.000807% 13/1,610,208 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,854
European (non-Finnish)	0.00102%	98,043

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.Gln245Pro
Coding: c.734A>C
MANE Select: NM_152617
Type: single nucleotide variant
Location: chr3:196475259 (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 245: the 'disordered' region

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.Gln245Ter Pathogenic ★ 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-gln245pro (accessed [today's date]).

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