Is PCDH15 p.Pro439fs (c.1316del) pathogenic?

PCDH15 p.Pro439fs (c.1316del) is classified Likely pathogenic in PCDH15 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-27). No gnomAD frequency available for this variant; Associated with Usher syndrome type 1D.

What condition is associated with PCDH15 p.Pro439fs (c.1316del)?

PCDH15 p.Pro439fs (c.1316del) is associated with Usher syndrome type 1D (ClinVar).

How common is PCDH15 p.Pro439fs (c.1316del) in the general population?

PCDH15 p.Pro439fs (c.1316del) is no gnomAD frequency available for this variant (gnomAD).

PCDH15 p.Pro439fs

c.1316del · rs2539510842 · VCV1726615

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Usher syndrome type 1D

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 12 of 38
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.083	phastCons 0.95

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: PCDH15
Protein: p.Pro439fs
Coding: c.1316del
MANE Select: NM_001384140
dbSNP: rs2539510842
Type: Deletion
Location: chr10:54185258 (GRCh38)
Gene constraint: LOEUF 0.819 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 66.05 · 8 PDB
Residue 439: the cadherin 4 domain

Full PCDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 1D — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCDH15 c.706-3_717del Pathogenic/Likely pathogenic ★★ same condition
PCDH15 p.Asn1470fs Pathogenic/Likely pathogenic ★★ same condition
PCDH15 p.Asp677fs Pathogenic/Likely pathogenic ★★ same condition
PCDH15 p.Asp783fs Likely pathogenic ★★ same condition
PCDH15 p.Cys120fs Pathogenic/Likely pathogenic ★★ same condition
PCDH15 p.Leu363fs Pathogenic/Likely pathogenic ★★ same condition
PCDH15 p.Lys941fs Pathogenic/Likely pathogenic ★★ same condition
PCDH15 p.Thr702_Val703insTer Pathogenic/Likely pathogenic ★★ same condition

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/pcdh15-p-pro439fs (accessed [today's date]).

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