Is PCDH19 p.Asp481= (c.1443C>T) pathogenic?

PCDH19 p.Asp481= (c.1443C>T) is classified Likely benign in PCDH19 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-22). Very rare (popmax 0.000112%, nfe); Associated with developmental and epileptic encephalopathy, 9.

What condition is associated with PCDH19 p.Asp481= (c.1443C>T)?

PCDH19 p.Asp481= (c.1443C>T) is associated with developmental and epileptic encephalopathy, 9 (ClinVar).

How common is PCDH19 p.Asp481= (c.1443C>T) in the general population?

PCDH19 p.Asp481= (c.1443C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

PCDH19 p.Asp481=

c.1443C>T · rs1602636091 · VCV763486

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

developmental and epileptic encephalopathy, 9

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.37	GERP -4.5, phastCons 0.027
Overall
CADD	3.664	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,506 alleles

Overall 8.25e-05% 1/1,211,920 alleles · very rare exomes 1/1,098,121 · genomes 0/113,799 · joint denominator

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: PCDH19
Protein: p.Asp481=
Coding: c.1443C>T
MANE Select: NM_001184880
dbSNP: rs1602636091
Type: single nucleotide variant
Location: chrX:100407155 (GRCh38)
Structure: AlphaFold pLDDT 68.50 · 1 PDB
Residue 481: a UniProt-annotated variant site (in dee9); a binding site; 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.Asp481Gly Likely pathogenic ★ same residue
PCDH19 p.Asp481Glu Uncertain significance ★ ⚠ same residue
PCDH19 p.Asp481fs Pathogenic ★ same residue
PCDH19 p.Asp481Asn Pathogenic ★ same residue
PCDH19 c.2675+1G>T Pathogenic/Likely pathogenic ★★ same condition
PCDH19 c.2675+2T>C Pathogenic ★★ same condition
PCDH19 p.Arg198Leu Pathogenic/Likely pathogenic ★★ same condition
PCDH19 p.Arg207Ter 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-asp481 (accessed [today's date]).

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