Is CDH11 p.Trp55Ser (c.164G>C) pathogenic?

CDH11 p.Trp55Ser (c.164G>C) is classified Pathogenic in CDH11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-01). AlphaMissense: likely pathogenic (0.9955); Absent from gnomAD v4.1; Associated with Teebi hypertelorism syndrome 2.

What condition is associated with CDH11 p.Trp55Ser (c.164G>C)?

CDH11 p.Trp55Ser (c.164G>C) is associated with Teebi hypertelorism syndrome 2 (ClinVar).

How common is CDH11 p.Trp55Ser (c.164G>C) in the general population?

CDH11 p.Trp55Ser (c.164G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH11 p.Trp55Ser (c.164G>C)?

AlphaMissense predicts likely pathogenic (score 0.9955) — an in-silico prediction, not a clinical call.

CDH11 p.Trp55Ser

c.164G>C · rs2142528709 · VCV1339267

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9955 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Teebi hypertelorism syndrome 2

Computational evidence

Protein change
AlphaMissense	0.9955	likely pathogenic ✓ concordant with ClinVar · top 6% in CDH11
REVEL	0.548	indeterminate
SaProt	LLR -13.21	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 13 kb · p 3.9e-10 · regional, not allelic
Overall
CADD	32.0	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: CDH11
Protein: p.Trp55Ser
Coding: c.164G>C
MANE Select: NM_001797
dbSNP: rs2142528709
Type: single nucleotide variant
Location: chr16:65004706 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 55: a UniProt-annotated variant site (in tbhs2; results in loss of cell adhesion as shown by a cell-substrate adhesion assay); the cadherin 1 domain

Full CDH11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Teebi hypertelorism syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH11 p.Asp260Asn Pathogenic/Likely pathogenic ★★ same condition
CDH11 p.Asp718Asn Uncertain significance ★★ ⚠ same condition
CDH11 p.Gly327Trp Likely pathogenic ★ same condition
CDH11 p.Glu534Gln Uncertain significance ★ same condition
CDH11 p.Met382Thr Uncertain significance ★ ⚠ same condition
CDH11 p.Asp260Glu Pathogenic same condition
CDH11 p.Glu279Gln Pathogenic same condition
CDH11 p.Leu77Phe Likely pathogenic same condition

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/cdh11-p-trp55ser (accessed [today's date]).

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