Is CDHR1 p.Pro261fs (c.782del) pathogenic?

CDHR1 p.Pro261fs (c.782del) is classified Pathogenic in CDHR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-15). Very rare (popmax 0.00133%, afr).

How common is CDHR1 p.Pro261fs (c.782del) in the general population?

CDHR1 p.Pro261fs (c.782del) is very rare (popmax 0.00133%, afr) (gnomAD).

CDHR1 p.Pro261fs

c.782del · rs1842160172 · VCV838072

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 8 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.29	GERP -1.9, phastCons 0.89

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,054 alleles

Overall 6.84e-05% 1/1,461,888 alleles · very rare

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: CDHR1
Protein: p.Pro261fs
Coding: c.782del
MANE Select: NM_033100
dbSNP: rs1842160172
Type: Deletion
Location: chr10:84203121 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 261: the cadherin 3 domain

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDHR1 p.Pro261Leu Uncertain significance ★★ ⚠ same residue
CDHR1 p.Pro261= Conflicting classifications of pathogenicity ★ same residue
CDHR1 p.Pro261Ser Uncertain significance ★ same residue
CDHR1 p.Asp238fs Pathogenic/Likely pathogenic ★★ same type
CDHR1 p.Asp696fs Pathogenic ★★ same type
CDHR1 p.Cys4fs Likely pathogenic ★★ same type
CDHR1 p.Glu264fs Likely pathogenic ★★ same type
CDHR1 p.Glu99fs Pathogenic ★★ 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/cdhr1-p-pro261fs (accessed [today's date]).

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