Is CTRB2 p.Glu96Lys (c.286G>A) pathogenic?

CTRB2 p.Glu96Lys (c.286G>A) is classified Uncertain significance in CTRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.2165); Absent from gnomAD v4.1.

How common is CTRB2 p.Glu96Lys (c.286G>A) in the general population?

CTRB2 p.Glu96Lys (c.286G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTRB2 p.Glu96Lys (c.286G>A)?

AlphaMissense predicts likely benign (score 0.2165) — an in-silico prediction, not a clinical call.

CTRB2 p.Glu96Lys

c.286G>A · VCV4657539

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2165 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2165	likely benign
REVEL	0.596	indeterminate
SaProt	LLR -13.79	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 2.2, phastCons 0.94
Regional constraint	o/e 0.09	constrained · MANE · 1,077 bp · p 4.7e-13 · regional, not allelic
Overall
CADD	20.6	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: CTRB2
Protein: p.Glu96Lys
Coding: c.286G>A
MANE Select: NM_001025200
Type: single nucleotide variant
Location: chr16:75205771 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 91.79
Residue 96: the peptidase s1 domain; a disulfide bond

Full CTRB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTRB2 p.Glu96Gly Uncertain significance ★ ⚠ same residue
CTRB2 p.Ala11Thr Uncertain significance ★ ⚠ same type
CTRB2 p.Ala138Thr Uncertain significance ★ ⚠ same type
CTRB2 p.Ala244Thr Uncertain significance ★ ⚠ same type
CTRB2 p.Arg131His Uncertain significance ★ ⚠ same type
CTRB2 p.Arg236Cys Uncertain significance ★ ⚠ same type
CTRB2 p.Arg236His Uncertain significance ★ ⚠ same type
CTRB2 p.Arg248Cys 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/ctrb2-p-glu96lys (accessed [today's date]).

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