Is CBY2 p.Ser47Arg (c.141T>A) pathogenic?

CBY2 p.Ser47Arg (c.141T>A) is classified Uncertain significance in CBY2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: ambiguous (0.3483); Absent from gnomAD v4.1.

How common is CBY2 p.Ser47Arg (c.141T>A) in the general population?

CBY2 p.Ser47Arg (c.141T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CBY2 p.Ser47Arg (c.141T>A)?

AlphaMissense predicts ambiguous (score 0.3483) — an in-silico prediction, not a clinical call.

CBY2 p.Ser47Arg

c.141T>A · VCV4648830

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3483 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3483	ambiguous
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.85	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.3	GERP -1.2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 12 kb · p 0.035 · regional, not allelic
Overall
CADD	16.22	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CBY2
Protein: p.Ser47Arg
Coding: c.141T>A
MANE Select: NM_152719
Type: single nucleotide variant
Location: chr13:45702840 (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-ser47arg (accessed [today's date]).

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