Is CDHR1 p.Ser489fs (c.1463dup) pathogenic?

CDHR1 p.Ser489fs (c.1463dup) is classified Pathogenic in CDHR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-04-06). Absent from gnomAD.

How common is CDHR1 p.Ser489fs (c.1463dup) in the general population?

CDHR1 p.Ser489fs (c.1463dup) is absent from gnomAD (gnomAD).

CDHR1 p.Ser489fs

c.1463dup · rs756678484 · VCV1069264

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 13 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -4.9	GERP -5.3

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDHR1
Protein: p.Ser489fs
Coding: c.1463dup
MANE Select: NM_033100
dbSNP: rs756678484
Type: Duplication
Location: chr10:84211138 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 489: the cadherin 5 domain

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

Similar variants

CDHR1 p.Asn176fs Pathogenic ★★ same type
CDHR1 p.Thr448fs Pathogenic/Likely pathogenic ★★ same type
CDHR1 c.958_963+2dup Uncertain significance ★★ same type
CDHR1 p.Leu566fs Pathogenic ★ same type
CDHR1 p.Lys556fs Pathogenic ★ same type
CDHR1 p.Ala560dup Uncertain significance ★ same type
CDHR1 p.Asn731Ter Uncertain significance ★ same type
CDHR1 p.Met709_Ala710insLysAlaValGlyValLeuAlaGlyThrMet 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/cdhr1-p-ser489fs (accessed [today's date]).

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