Is CDHR3 p.Asp231Asn (c.691G>A) pathogenic?

CDHR3 p.Asp231Asn (c.691G>A) is classified Uncertain significance in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-31). AlphaMissense: ambiguous (0.3491); Very rare (popmax 0.0012%, nfe).

How common is CDHR3 p.Asp231Asn (c.691G>A) in the general population?

CDHR3 p.Asp231Asn (c.691G>A) is very rare (popmax 0.0012%, nfe) (gnomAD).

What do computational predictors say about CDHR3 p.Asp231Asn (c.691G>A)?

AlphaMissense predicts ambiguous (score 0.3491) — an in-silico prediction, not a clinical call.

CDHR3 p.Asp231Asn

c.691G>A · rs535238500 · VCV2532209

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3491 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0012%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3491	ambiguous
REVEL	0.404	indeterminate
SaProt	LLR -10.14	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 5.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.92 · regional, not allelic
Overall
CADD	25.7	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 0.0012% European (non-Finnish) · 14/1,164,844 alleles

Filtering AF 0.000697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000546%

Overall 0.000941% 15/1,594,498 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0012%	83,203
South Asian	0.00111%	89,890

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.Asp231Asn
Coding: c.691G>A
MANE Select: NM_152750
dbSNP: rs535238500
Type: single nucleotide variant
Location: chr7:105996332 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 231: the cadherin 2 domain

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

Similar variants

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
CDHR3 p.Ala541Val 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-asp231asn (accessed [today's date]).

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