Is CENPB p.Pro157Ala (c.469C>G) pathogenic?

CENPB p.Pro157Ala (c.469C>G) is classified Uncertain significance in CENPB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.0567); Very rare (popmax 0.00563%, eas).

How common is CENPB p.Pro157Ala (c.469C>G) in the general population?

CENPB p.Pro157Ala (c.469C>G) is very rare (popmax 0.00563%, eas) (gnomAD).

What do computational predictors say about CENPB p.Pro157Ala (c.469C>G)?

AlphaMissense predicts likely benign (score 0.0567) — an in-silico prediction, not a clinical call.

CENPB p.Pro157Ala

c.469C>G · rs769161961 · VCV2588186

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0567 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00563%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0567	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -6.15	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 5.3	GERP -1.2, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 1,400 bp · p 0.00023 · regional, not allelic
Overall
CADD	17.5	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 0.00563% East Asian · 2/35,522 alleles

Filtering AF 0.000933% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000349%

Overall 0.000209% 3/1,437,768 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00563%	17,761
South Asian	0.00146%	68,468

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: CENPB
Protein: p.Pro157Ala
Coding: c.469C>G
MANE Select: NM_001810
dbSNP: rs769161961
Type: single nucleotide variant
Location: chr20:3786015 (GRCh38)
Gene constraint: LOEUF 0.828 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.88 · 4 PDB
Residue 157: the 'disordered' region

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

Similar variants

CENPB p.Pro157Leu Uncertain significance ★ ⚠ same residue
CENPB p.Ala174Pro Uncertain significance ★ ⚠ same type
CENPB p.Ala231Thr Uncertain significance ★ ⚠ same type
CENPB p.Ala301Pro Uncertain significance ★ ⚠ same type
CENPB p.Ala345Thr Uncertain significance ★ ⚠ same type
CENPB p.Ala381Val Uncertain significance ★ ⚠ same type
CENPB p.Arg175Gln Uncertain significance ★ ⚠ same type
CENPB p.Arg219Cys 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/cenpb-p-pro157ala (accessed [today's date]).

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