Is PCDH19 p.Arg519fs (c.1556del) pathogenic?

PCDH19 p.Arg519fs (c.1556del) is classified Likely pathogenic in PCDH19 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-29). No gnomAD frequency available for this variant; Associated with developmental and epileptic encephalopathy, 9.

What condition is associated with PCDH19 p.Arg519fs (c.1556del)?

PCDH19 p.Arg519fs (c.1556del) is associated with developmental and epileptic encephalopathy, 9 (ClinVar).

How common is PCDH19 p.Arg519fs (c.1556del) in the general population?

PCDH19 p.Arg519fs (c.1556del) is no gnomAD frequency available for this variant (gnomAD).

PCDH19 p.Arg519fs

c.1556del · rs2147538465 · VCV1324859

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

developmental and epileptic encephalopathy, 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.33	GERP -2.8, phastCons 1

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: PCDH19
Protein: p.Arg519fs
Coding: c.1556del
MANE Select: NM_001184880
dbSNP: rs2147538465
Type: Deletion
Location: chrX:100407042 (GRCh38)
Structure: AlphaFold pLDDT 68.50 · 1 PDB
Residue 519: a UniProt-annotated variant site (in dee9); the cadherin 5 domain

Full PCDH19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental and epileptic encephalopathy, 9 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PCDH19 p.Arg519Ter Pathogenic ★ same residue
PCDH19 p.Asn559fs Pathogenic ★★ same condition
PCDH19 p.Asn875fs Pathogenic ★★ same condition
PCDH19 p.Asp45fs Pathogenic ★★ same condition
PCDH19 p.Glu354fs Pathogenic ★★ same condition
PCDH19 p.Gly690fs Pathogenic/Likely pathogenic ★★ same condition
PCDH19 p.Pro364fs Pathogenic ★★ same condition
PCDH19 p.Pro561fs 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/pcdh19-p-arg519fs (accessed [today's date]).

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