Is CDH11 p.Ser373Ala (c.1117T>G) pathogenic?

CDH11 p.Ser373Ala (c.1117T>G) is classified Benign in CDH11 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-07-14). AlphaMissense: likely benign (0.0565); Common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Elsahy-Waters syndrome.

What condition is associated with CDH11 p.Ser373Ala (c.1117T>G)?

CDH11 p.Ser373Ala (c.1117T>G) is associated with Elsahy-Waters syndrome (ClinVar).

What do computational predictors say about CDH11 p.Ser373Ala (c.1117T>G)?

AlphaMissense predicts likely benign (score 0.0565) — an in-silico prediction, not a clinical call.

CDH11 p.Ser373Ala

Q: How common is CDH11 p.Ser373Ala (c.1117T>G) in the general population?

CDH11 p.Ser373Ala (c.1117T>G) is common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1117T>G · rs35213 · VCV1192549

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0565 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 99.8%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Elsahy-Waters syndrome

Computational evidence

Protein change
AlphaMissense	0.0565	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -6.66	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 2.2	GERP 0.6, phastCons 0.97
Regional constraint	o/e 0.90	unconstrained · MANE · 44 kb · p 0.01 · regional, not allelic
Overall
CADD	13.2	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 99.8% East Asian · 44,784/44,858 alleles

Filtering AF 99.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.7%

Overall 80.5% 1,299,018/1,613,556 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	99.8%	1
Amishnot grpmax-eligible	90.5%	1
South Asian	88.7%	1
Ashkenazi Jewishnot grpmax-eligible	82.4%	1
European (non-Finnish)	81.4%	1
Admixed American	81.2%	1
Middle Eastern	80.5%	1
Finnishnot grpmax-eligible	80%	1
Remaining individualsnot grpmax-eligible	79.8%	1
African / African-American	44.6%	2

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.Ser373Ala
Coding: c.1117T>G
MANE Select: NM_001797
dbSNP: rs35213
Type: single nucleotide variant
Location: chr16:64982184 (GRCh38)
Gene constraint: LOEUF 0.249 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.65
Residue 373: a UniProt-annotated variant site (in esws); a UniProt-annotated variant site (in); the cadherin 3 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

Similar variants

CDH11 p.Ser373Thr Uncertain significance ★ ⚠ same residue
CDH11 p.Asp260Asn Pathogenic/Likely pathogenic ★★ 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
CDH11 p.Ser315= 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-ser373ala (accessed [today's date]).

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