Is CDHR3 p.Pro388Arg (c.1163C>G) pathogenic?

CDHR3 p.Pro388Arg (c.1163C>G) is classified Uncertain significance in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-26). AlphaMissense: likely pathogenic (0.6673); Absent from gnomAD v4.1.

How common is CDHR3 p.Pro388Arg (c.1163C>G) in the general population?

CDHR3 p.Pro388Arg (c.1163C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDHR3 p.Pro388Arg (c.1163C>G)?

AlphaMissense predicts likely pathogenic (score 0.6673) — an in-silico prediction, not a clinical call.

CDHR3 p.Pro388Arg

c.1163C>G · rs2485447968 · VCV2479418

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6673 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6673	likely pathogenic · top 9% in CDHR3
REVEL	0.258	benign-leaning
SaProt	LLR -2.65	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 4.8, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.92 · regional, not allelic
Overall
CADD	24.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDHR3
Protein: p.Pro388Arg
Coding: c.1163C>G
MANE Select: NM_152750
dbSNP: rs2485447968
Type: single nucleotide variant
Location: chr7:106012970 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 388: 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.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-pro388arg (accessed [today's date]).

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