Is TP63 p.Phe565fs (c.1693_1694del) pathogenic?

TP63 p.Phe565fs (c.16931694del) is classified Pathogenic in TP63 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-08-01). No gnomAD frequency available for this variant; Associated with limb-mammary syndrome.

What condition is associated with TP63 p.Phe565fs (c.1693_1694del)?

TP63 p.Phe565fs (c.1693_1694del) is associated with limb-mammary syndrome (ClinVar).

How common is TP63 p.Phe565fs (c.1693_1694del) in the general population?

TP63 p.Phe565fs (c.1693_1694del) is no gnomAD frequency available for this variant (gnomAD).

TP63 p.Phe565fs

c.1693_1694del · rs2108864814 · VCV6538

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

limb-mammary 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	predicted	premature termination codon in exon 13 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.9, 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.Phe565fs
Coding: c.1693_1694del
MANE Select: NM_003722
dbSNP: rs2108864814
Type: Deletion
Location: chr3:189890828 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 565: the sam domain; an α-helix

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

Disease context

limb-mammary syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP63 c.192-9_192-8del Benign/Likely benign ★★ same condition
TP63 p.Phe565Leu Pathogenic ★ ⚠ same residue
TP63 p.Phe565Val Pathogenic ★ same residue
TP63 p.Ser621fs Pathogenic ★ same condition
TP63 p.Arg243Trp Pathogenic ★★ same condition
TP63 p.Arg343Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg655Ter Likely pathogenic ★★ same condition
TP63 c.1507+6_1507+7del Uncertain significance ★★ 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-phe565fs (accessed [today's date]).

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