Is CDHR3 p.Gln399= (c.1197G>A) pathogenic?

CDHR3 p.Gln399= (c.1197G>A) is classified Benign in CDHR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-05-08). Common (popmax 5.31%, afr) — too common for a highly-penetrant pathogenic allele.

CDHR3 p.Gln399=

Q: How common is CDHR3 p.Gln399= (c.1197G>A) in the general population?

CDHR3 p.Gln399= (c.1197G>A) is common (popmax 5.31%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1197G>A · rs79686695 · VCV768192

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.31%, afr) — too common for a highly-penetrant pathogenic allele

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 8.5	GERP 4.8, phastCons 1
Overall
CADD	10.95	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.31% African / African-American · 3,973/74,798 alleles

Filtering AF 5.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.12%

Overall 0.29% 4,659/1,609,180 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.31%	19
Admixed American	0.491%	204
Remaining individualsnot grpmax-eligible	0.44%	227
Middle Eastern	0.364%	274
South Asian	0.0111%	9,011
European (non-Finnish)	0.00764%	13,089

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.Gln399=
Coding: c.1197G>A
MANE Select: NM_152750
dbSNP: rs79686695
Type: single nucleotide variant
Location: chr7:106013004 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 399: the cadherin 4 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.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
CDHR3 p.Ala820Val 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-gln399 (accessed [today's date]).

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