Is CBY2 p.Pro51Ser (c.151C>T) pathogenic?

CBY2 p.Pro51Ser (c.151C>T) is classified Uncertain significance in CBY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.1732); Very rare (popmax 0.005%, amr).

How common is CBY2 p.Pro51Ser (c.151C>T) in the general population?

CBY2 p.Pro51Ser (c.151C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CBY2 p.Pro51Ser (c.151C>T)?

AlphaMissense predicts likely benign (score 0.1732) — an in-silico prediction, not a clinical call.

CBY2 p.Pro51Ser

c.151C>T · rs763800825 · VCV2463871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1732 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1732	likely benign
REVEL	0.124	moderately benign-leaning
SaProt	LLR -6.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 0.5, phastCons 0.99
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.035 · regional, not allelic
Overall
CADD	19.34	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 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000719%

Overall 0.0013% 21/1,610,824 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0016%	62,394
European (non-Finnish)	0.00144%	69,244

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: CBY2
Protein: p.Pro51Ser
Coding: c.151C>T
MANE Select: NM_152719
dbSNP: rs763800825
Type: single nucleotide variant
Location: chr13:45702850 (GRCh38)
Gene constraint: LOEUF 1.393 · pLI <0.01 · ClinGen HI dosage-sensitivity unlikely (gnomAD)
Structure: AlphaFold pLDDT 63.75

Full CBY2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CBY2 p.Ala163Thr Uncertain significance ★ ⚠ same type
CBY2 p.Ala205Asp Uncertain significance ★ ⚠ same type
CBY2 p.Ala214Thr Uncertain significance ★ ⚠ same type
CBY2 p.Ala214Val Uncertain significance ★ ⚠ same type
CBY2 p.Ala224Glu Uncertain significance ★ ⚠ same type
CBY2 p.Ala269Val Uncertain significance ★ ⚠ same type
CBY2 p.Ala76Thr Uncertain significance ★ ⚠ same type
CBY2 p.Arg141His 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/cby2-p-pro51ser (accessed [today's date]).

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