Is CDH11 p.Asp260Asn (c.778G>A) pathogenic?

CDH11 p.Asp260Asn (c.778G>A) is classified Pathogenic/Likely pathogenic in CDH11 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-03-05). AlphaMissense: likely pathogenic (0.9631); Very rare (popmax 8.48e-05%, nfe); Associated with Elsahy-Waters syndrome.

What condition is associated with CDH11 p.Asp260Asn (c.778G>A)?

CDH11 p.Asp260Asn (c.778G>A) is associated with Elsahy-Waters syndrome, Teebi hypertelorism syndrome 2 (ClinVar).

How common is CDH11 p.Asp260Asn (c.778G>A) in the general population?

CDH11 p.Asp260Asn (c.778G>A) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDH11 p.Asp260Asn (c.778G>A)?

AlphaMissense predicts likely pathogenic (score 0.9631) — an in-silico prediction, not a clinical call.

CDH11 p.Asp260Asn

c.778G>A · rs2142492118 · VCV1339269

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9631 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Elsahy-Waters syndrome

Computational evidence

Protein change
AlphaMissense	0.9631	likely pathogenic ✓ concordant with ClinVar
REVEL	0.525	indeterminate
SaProt	LLR -8.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 13 kb · p 3.9e-10 · regional, not allelic
Overall
CADD	33.0	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,758 alleles

Overall 6.84e-05% 1/1,461,502 alleles · very rare

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: CDH11
Protein: p.Asp260Asn
Coding: c.778G>A
MANE Select: NM_001797
dbSNP: rs2142492118
Type: single nucleotide variant
Location: chr16:64991801 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 260: a UniProt-annotated variant site (in esws); a UniProt-annotated variant site (in tbhs2); a UniProt-annotated variant site (in tbhs2; results in decreased cell adhesion as shown by a cell-substrate adhesion assay); the cadherin 2 domain

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

Disease context

Elsahy-Waters syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Teebi hypertelorism syndrome 2

Similar variants

CDH11 p.Asp260His Likely pathogenic ★ same residue
CDH11 p.Asp260Glu Pathogenic same residue
CDH11 p.Asp718Asn Uncertain significance ★★ ⚠ same condition
CDH11 c.1253+43G>C Benign ★★ same condition
CDH11 c.1642+20C>T Benign ★★ same condition
CDH11 c.644-11T>C Benign ★★ same condition
CDH11 c.811+13A>G Benign ★★ same condition
CDH11 p.Met275Ile Benign ★★ ⚠ 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-asp260asn (accessed [today's date]).

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