Is CDHR3 p.Ser213= (c.639T>C) pathogenic?

CDHR3 p.Ser213= (c.639T>C) is classified Likely benign in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). Very rare (popmax 0.00225%, eas).

How common is CDHR3 p.Ser213= (c.639T>C) in the general population?

CDHR3 p.Ser213= (c.639T>C) is very rare (popmax 0.00225%, eas) (gnomAD).

CDHR3 p.Ser213=

c.639T>C · rs1489788568 · VCV2657920

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00225%, eas)

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 -1.9	GERP 0.002
Overall
CADD	2.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00225% East Asian · 1/44,422 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000313% 5/1,598,444 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00225%	44,422
European (non-Finnish)	0.000343%	291,832

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: CDHR3
Protein: p.Ser213=
Coding: c.639T>C
MANE Select: NM_152750
dbSNP: rs1489788568
Type: single nucleotide variant
Location: chr7:105996280 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 213: the cadherin 2 domain

Full CDHR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR3 p.Ser213Arg Uncertain significance ★ ⚠ same residue
CDHR3 c.1653+3G>A Benign/Likely benign ★★ same type
CDHR3 p.Arg603Cys Likely benign ★★ ⚠ same type
CDHR3 p.Asp337= Benign ★★ same type
CDHR3 p.Gln399= Benign ★★ same type
CDHR3 p.Ala148Ser Uncertain significance ★ ⚠ same type
CDHR3 p.Ala158Asp Uncertain significance ★ ⚠ same type
CDHR3 p.Ala541Asp 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/cdhr3-p-ser213 (accessed [today's date]).

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