Is CTRB2 p.Trp5Leu (c.14G>T) pathogenic?

CTRB2 p.Trp5Leu (c.14G>T) is classified Uncertain significance in CTRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-12). AlphaMissense: likely benign (0.0862); Rare (popmax 0.277%, amr).

How common is CTRB2 p.Trp5Leu (c.14G>T) in the general population?

CTRB2 p.Trp5Leu (c.14G>T) is rare (popmax 0.277%, amr) (gnomAD).

What do computational predictors say about CTRB2 p.Trp5Leu (c.14G>T)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

CTRB2 p.Trp5Leu

c.14G>T · rs148293871 · VCV2385161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.277%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.472	indeterminate
SaProt	LLR -3.86	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 3.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,158 bp · p 0.067 · regional, not allelic
Overall
CADD	20.3	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 0.277% Admixed American · 142/51,280 alleles

Filtering AF 0.24% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.226%

Overall 0.135% 2,108/1,558,852 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.277%	361
European (non-Finnish)	0.163%	615
Remaining individualsnot grpmax-eligible	0.106%	944
Middle Eastern	0.0334%	2,997
African / African-American	0.0324%	3,086
Finnishnot grpmax-eligible	0.00499%	20,032
South Asian	0.00118%	84,640

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.Trp5Leu
Coding: c.14G>T
MANE Select: NM_001025200
dbSNP: rs148293871
Type: single nucleotide variant
Location: chr16:75207128 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 91.79

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-trp5leu (accessed [today's date]).

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