Is CDHR3 p.Val447Ile (c.1339G>A) pathogenic?

CDHR3 p.Val447Ile (c.1339G>A) is classified Likely benign in CDHR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-13). AlphaMissense: likely benign (0.0593); Ultra-rare (popmax 0.023%, nfe).

How common is CDHR3 p.Val447Ile (c.1339G>A) in the general population?

CDHR3 p.Val447Ile (c.1339G>A) is ultra-rare (popmax 0.023%, nfe) (gnomAD).

What do computational predictors say about CDHR3 p.Val447Ile (c.1339G>A)?

AlphaMissense predicts likely benign (score 0.0593) — an in-silico prediction, not a clinical call.

CDHR3 p.Val447Ile

c.1339G>A · rs193279079 · VCV2298806

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0593 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0593	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -6.31	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 1.2	GERP 0.4, phastCons 0.27
Regional constraint	o/e 1.00	unconstrained · MANE · 69 kb · p 0.92 · regional, not allelic
Overall
CADD	3.343	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 0.023% European (non-Finnish) · 270/1,175,924 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.019% 305/1,608,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.023%	4,355
Remaining individualsnot grpmax-eligible	0.0209%	4,795
Middle Eastern	0.0165%	6,052
East Asian	0.0156%	6,407
African / African-American	0.0107%	9,366
South Asian	0.00441%	22,666
Admixed American	0.00167%	59,872
Finnishnot grpmax-eligible	0.00157%	63,860

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.Val447Ile
Coding: c.1339G>A
MANE Select: NM_152750
dbSNP: rs193279079
Type: single nucleotide variant
Location: chr7:106015938 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 447: 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-val447ile (accessed [today's date]).

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