Is CDHR2 p.Trp47Ser (c.140G>C) pathogenic?

CDHR2 p.Trp47Ser (c.140G>C) is classified Uncertain significance in CDHR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-28). AlphaMissense: likely benign (0.2593); Absent from gnomAD v4.1.

How common is CDHR2 p.Trp47Ser (c.140G>C) in the general population?

CDHR2 p.Trp47Ser (c.140G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDHR2 p.Trp47Ser (c.140G>C)?

AlphaMissense predicts likely benign (score 0.2593) — an in-silico prediction, not a clinical call.

CDHR2 p.Trp47Ser

c.140G>C · VCV4840750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2593 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2593	likely benign
REVEL	0.318	indeterminate
SaProt	LLR -1.95	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 7.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 19 kb · p 0.025 · regional, not allelic
Overall
CADD	21.4	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

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: CDHR2
Protein: p.Trp47Ser
Coding: c.140G>C
MANE Select: NM_017675
Type: single nucleotide variant
Location: chr5:176568693 (GRCh38)
Gene constraint: LOEUF 0.88 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.84 · 2 PDB
Residue 47: the cadherin 1 domain; a β-strand

Full CDHR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR2 p.Ala1162Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala121Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala13Val Uncertain significance ★ ⚠ same type
CDHR2 p.Ala415Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala423Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala512Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala652Thr Uncertain significance ★ ⚠ same type
CDHR2 p.Ala656Thr 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/cdhr2-p-trp47ser (accessed [today's date]).

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