Is TP63 p.His615fs (c.1833_1843dup) pathogenic?

TP63 p.His615fs (c.18331843dup) is classified Pathogenic in TP63 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-01-01). No gnomAD frequency available for this variant; Associated with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome.

What condition is associated with TP63 p.His615fs (c.1833_1843dup)?

TP63 p.His615fs (c.1833_1843dup) is associated with ankyloblepharon-ectodermal defects-cleft lip/palate syndrome, Rapp-Hodgkin syndrome (ClinVar).

How common is TP63 p.His615fs (c.1833_1843dup) in the general population?

TP63 p.His615fs (c.1833_1843dup) is no gnomAD frequency available for this variant (gnomAD).

TP63 p.His615fs

c.1833_1843dup · rs2474724873 · VCV6553

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

ankyloblepharon-ectodermal defects-cleft lip/palate syndrome

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 LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.57	GERP -2, 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: TP63
Protein: p.His615fs
Coding: c.1833_1843dup
MANE Select: NM_003722
dbSNP: rs2474724873
Type: Duplication
Location: chr3:189894286 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 615: a β-strand; a UniProt-annotated variant site (in pof21; results in increased transcriptional activation in luciferase reporter assays; affects oligomerization); a UniProt-annotated variant site (in pof21); the 'transactivation inhibition' region

Full TP63 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ankyloblepharon-ectodermal defects-cleft lip/palate syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rapp-Hodgkin syndrome

Similar variants

TP63 p.Leu116fs Likely pathogenic ★ same condition
TP63 p.Leu287fs Likely pathogenic ★ same condition
TP63 p.His615Tyr Uncertain significance ★ ⚠ same residue
TP63 p.Arg243Trp Pathogenic ★★ same condition
TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg343Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg343Trp Pathogenic ★★ same condition
TP63 p.His247Arg 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/tp63-p-his615fs (accessed [today's date]).

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