Is CTRB2 p.Glu95Lys (c.283G>A) pathogenic?

CTRB2 p.Glu95Lys (c.283G>A) is classified Uncertain significance in CTRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-16). AlphaMissense: likely benign (0.1205); Ultra-rare (popmax 0.0738%, mid).

How common is CTRB2 p.Glu95Lys (c.283G>A) in the general population?

CTRB2 p.Glu95Lys (c.283G>A) is ultra-rare (popmax 0.0738%, mid) (gnomAD).

What do computational predictors say about CTRB2 p.Glu95Lys (c.283G>A)?

AlphaMissense predicts likely benign (score 0.1205) — an in-silico prediction, not a clinical call.

CTRB2 p.Glu95Lys

c.283G>A · rs901293366 · VCV2392079

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1205 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0738%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1205	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -5.11	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -4.4
Regional constraint	o/e 0.09	constrained · MANE · 1,077 bp · p 4.7e-13 · regional, not allelic
Overall
CADD	14.1	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 0.0738% Middle Eastern · 2/2,710 alleles

Filtering AF 0.0189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00706% 61/864,542 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0738%	1,355
South Asian	0.0294%	3,407
African / African-American	0.0131%	7,656
European (non-Finnish)	0.0061%	16,386
Remaining individualsnot grpmax-eligible	0.00265%	37,766

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: CTRB2
Protein: p.Glu95Lys
Coding: c.283G>A
MANE Select: NM_001025200
dbSNP: rs901293366
Type: single nucleotide variant
Location: chr16:75205774 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 91.79
Residue 95: 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.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
CTRB2 p.Asn167Tyr 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-glu95lys (accessed [today's date]).

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