Is CDH15 p.Ser341= (c.1023G>A) pathogenic?

CDH15 p.Ser341= (c.1023G>A) is classified Benign in CDH15 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2021-07-14). Common (popmax 33.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, autosomal dominant 3.

What condition is associated with CDH15 p.Ser341= (c.1023G>A)?

CDH15 p.Ser341= (c.1023G>A) is associated with intellectual disability, autosomal dominant 3 (ClinVar).

CDH15 p.Ser341=

Q: How common is CDH15 p.Ser341= (c.1023G>A) in the general population?

CDH15 p.Ser341= (c.1023G>A) is common (popmax 33.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1023G>A · rs72819366 · VCV128641

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 33.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, autosomal dominant 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -2.8
Overall
CADD	0.131	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 33.1% East Asian · 14,824/44,810 alleles

Filtering AF 32.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.5%

Overall 19.3% 311,823/1,612,062 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	33.1%	3
South Asian	24.2%	4
European (non-Finnish)	19.9%	5
Middle Eastern	19.3%	5
Remaining individualsnot grpmax-eligible	18.7%	5
Finnishnot grpmax-eligible	17.7%	6
Ashkenazi Jewishnot grpmax-eligible	16.7%	6
Amishnot grpmax-eligible	12.4%	8
Admixed American	9.78%	10
African / African-American	6.5%	15

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: CDH15
Protein: p.Ser341=
Coding: c.1023G>A
MANE Select: NM_004933
dbSNP: rs72819366
Type: single nucleotide variant
Location: chr16:89190287 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 341: the cadherin 3 domain

Full CDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal dominant 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDH15 p.Ser341Pro Uncertain significance ★ ⚠ same residue
CDH15 p.Arg92Trp Uncertain significance ★★ ⚠ same condition
CDH15 p.Gly514Arg Uncertain significance ★★ ⚠ same condition
CDH15 p.Pro347Leu Uncertain significance ★★ ⚠ same condition
CDH15 p.Pro347Ser Uncertain significance ★★ ⚠ same condition
CDH15 p.Thr158Ala Uncertain significance ★★ ⚠ same condition
CDH15 p.Val43Leu Uncertain significance ★★ ⚠ same condition
CDH15 p.Ala122Val Likely 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/cdh15-p-ser341 (accessed [today's date]).

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