Is CTRB2 p.Ile114Thr (c.341T>C) pathogenic?

CTRB2 p.Ile114Thr (c.341T>C) is classified Uncertain significance in CTRB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). AlphaMissense: ambiguous (0.4138); Absent from gnomAD v4.1.

How common is CTRB2 p.Ile114Thr (c.341T>C) in the general population?

CTRB2 p.Ile114Thr (c.341T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTRB2 p.Ile114Thr (c.341T>C)?

AlphaMissense predicts ambiguous (score 0.4138) — an in-silico prediction, not a clinical call.

CTRB2 p.Ile114Thr

c.341T>C · VCV3498389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4138 · 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	0.4138	ambiguous
REVEL	0.261	benign-leaning
SaProt	LLR -6.66	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.8	GERP 0.24
Regional constraint	o/e 0.09	constrained · MANE · 1,077 bp · p 4.7e-13 · regional, not allelic
Overall
CADD	3.005	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.Ile114Thr
Coding: c.341T>C
MANE Select: NM_001025200
Type: single nucleotide variant
Location: chr16:75205488 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI 0.36 (gnomAD)
Structure: AlphaFold pLDDT 91.79
Residue 114: 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-ile114thr (accessed [today's date]).

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