Is CDH11 p.Arg32Gln (c.95G>A) pathogenic?

CDH11 p.Arg32Gln (c.95G>A) is classified Likely benign in CDH11 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-08-12). AlphaMissense: likely benign (0.0768); Very rare (popmax 0.00269%, afr); Associated with Moebius syndrome.

What condition is associated with CDH11 p.Arg32Gln (c.95G>A)?

CDH11 p.Arg32Gln (c.95G>A) is associated with Moebius syndrome (ClinVar).

How common is CDH11 p.Arg32Gln (c.95G>A) in the general population?

CDH11 p.Arg32Gln (c.95G>A) is very rare (popmax 0.00269%, afr) (gnomAD).

How is Moebius syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CDH11 p.Arg32Gln (c.95G>A)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

CDH11 p.Arg32Gln

c.95G>A · rs757142171 · VCV254106

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Moebius syndrome

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.04	moderately benign-leaning
SaProt	LLR -7.19	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.53, phastCons 0.8
Regional constraint	o/e 0.67	unconstrained · MANE · 13 kb · p 3.9e-10 · regional, not allelic
Overall
CADD	18.51	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 0.00269% African / African-American · 2/74,248 alleles

Filtering AF 0.000548% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000433%

Overall 0.00107% 17/1,591,554 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00269%	37,124
Admixed American	0.00173%	57,734
Finnishnot grpmax-eligible	0.00162%	61,820
South Asian	0.00112%	89,484
European (non-Finnish)	0.00103%	97,289

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.Arg32Gln
Coding: c.95G>A
MANE Select: NM_001797
dbSNP: rs757142171
Type: single nucleotide variant
Location: chr16:65004775 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65

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

Disease context

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

For Moebius syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Antenatal, Neonatal

Similar variants

CDH11 p.Arg32Trp Uncertain significance ★ ⚠ same residue
CDH11 p.Pro416Leu Likely benign ⚠ same condition
CDH11 p.Asp260Asn Pathogenic/Likely pathogenic ★★ same type
CDH11 p.Ala228Ser Uncertain significance ★★ ⚠ same type
CDH11 p.Arg556Trp Uncertain significance ★★ ⚠ same type
CDH11 p.Asp718Asn Uncertain significance ★★ ⚠ same type
CDH11 p.Gly45Arg Uncertain significance ★★ ⚠ same type
CDH11 p.Gly618Ser 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/cdh11-p-arg32gln (accessed [today's date]).

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