Is CDHR3 p.Pro439fs (c.1316del) pathogenic?

CDHR3 p.Pro439fs (c.1316del) is classified Uncertain significance in CDHR3 (ClinVar, Single submitter, 2 submitters). Rare (popmax 0.951%, eas).

How common is CDHR3 p.Pro439fs (c.1316del) in the general population?

CDHR3 p.Pro439fs (c.1316del) is rare (popmax 0.951%, eas) (gnomAD).

CDHR3 p.Pro439fs

c.1316del · rs201638418 · VCV1294432

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.951%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 10 of 19
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4	GERP 4.3, phastCons 0.96
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.951% East Asian · 426/44,806 alleles

Filtering AF 0.876% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.847%

Overall 0.0408% 657/1,609,176 alleles · rare exomes 594/1,457,160 · genomes 63/152,016 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.951%	105
Finnishnot grpmax-eligible	0.182%	550
Remaining individualsnot grpmax-eligible	0.0321%	3,118
South Asian	0.0134%	7,464
European (non-Finnish)	0.00671%	14,910
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,478
African / African-American	0.00267%	37,410
Admixed American	0.00168%	59,544

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.Pro439fs
Coding: c.1316del
MANE Select: NM_152750
dbSNP: rs201638418
Type: Deletion
Location: chr7:106015196 (GRCh38)
Gene constraint: LOEUF 1.087 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.08 · 3 PDB
Residue 439: the cadherin 4 domain

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

Similar variants

CDHR3 p.Pro439Thr Uncertain significance ★ ⚠ same residue

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-pro439fs (accessed [today's date]).

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