Is RAD23B p.Pro161Ser (c.481C>T) pathogenic?

RAD23B p.Pro161Ser (c.481C>T) is classified Uncertain significance in RAD23B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-13). AlphaMissense: likely benign (0.0604); Ultra-rare (popmax 0.0134%, eas).

How common is RAD23B p.Pro161Ser (c.481C>T) in the general population?

RAD23B p.Pro161Ser (c.481C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about RAD23B p.Pro161Ser (c.481C>T)?

AlphaMissense predicts likely benign (score 0.0604) — an in-silico prediction, not a clinical call.

RAD23B p.Pro161Ser

c.481C>T · rs781509755 · VCV3151027

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0604 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0604	likely benign
REVEL	0.117	moderately benign-leaning
SaProt	LLR -4.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 9,596 bp · p 0.17 · regional, not allelic
Overall
CADD	19.74	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 0.0134% East Asian · 6/44,888 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.000434% 7/1,613,616 alleles · ultra-rare exomes 5/1,461,462 · genomes 2/152,154 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,481
Remaining individualsnot grpmax-eligible	0.0016%	62,470

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: RAD23B
Protein: p.Pro161Ser
Coding: c.481C>T
MANE Select: NM_002874
dbSNP: rs781509755
Type: single nucleotide variant
Location: chr9:107306631 (GRCh38)
Gene constraint: LOEUF 0.224 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 12 PDB
Residue 161: the 'disordered' region

Full RAD23B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAD23B p.Lys151Glu Uncertain significance ★★ ⚠ same type
RAD23B p.Ala209Ser Uncertain significance ★ ⚠ same type
RAD23B p.Ala245Val Uncertain significance ★ ⚠ same type
RAD23B p.Ala259Thr Uncertain significance ★ ⚠ same type
RAD23B p.Ala38Gly Uncertain significance ★ ⚠ same type
RAD23B p.Arg308Gln Uncertain significance ★ ⚠ same type
RAD23B p.Asp170Gly Uncertain significance ★ ⚠ same type
RAD23B p.Asp219His Uncertain significance ★ ⚠ 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/rad23b-p-pro161ser (accessed [today's date]).

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