Is CDHR3 p.Arg328Ser (c.982C>A) pathogenic?

CDHR3 p.Arg328Ser (c.982C>A) is classified Uncertain significance in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-25). AlphaMissense: likely benign (0.25); Ultra-rare (popmax 0.032%, afr).

How common is CDHR3 p.Arg328Ser (c.982C>A) in the general population?

CDHR3 p.Arg328Ser (c.982C>A) is ultra-rare (popmax 0.032%, afr) (gnomAD).

What do computational predictors say about CDHR3 p.Arg328Ser (c.982C>A)?

AlphaMissense predicts likely benign (score 0.25) — an in-silico prediction, not a clinical call.

CDHR3 p.Arg328Ser

c.982C>A · rs749341687 · VCV2468734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.25 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.032%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.25	likely benign
REVEL	0.147	moderately benign-leaning
SaProt	LLR -7.41	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 1.8	GERP 5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.92 · regional, not allelic
Overall
CADD	18.81	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.032% African / African-American · 24/75,052 alleles

Filtering AF 0.022% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0187%

Overall 0.00204% 33/1,613,994 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.032%	3,127
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,621
Admixed American	0.00333%	30,013
European (non-Finnish)	0.00017%	589,943

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.Arg328Ser
Coding: c.982C>A
MANE Select: NM_152750
dbSNP: rs749341687
Type: single nucleotide variant
Location: chr7:106004617 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 328: the cadherin 3 domain

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

Similar variants

CDHR3 p.Arg328Cys Uncertain significance ★ ⚠ same residue
CDHR3 p.Arg328Leu Uncertain significance ★ ⚠ same residue
CDHR3 p.Arg328His Likely benign ★ ⚠ 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

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-arg328ser (accessed [today's date]).

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