Is TP63 p.Arg655Ter (c.1963C>T) pathogenic?

TP63 p.Arg655Ter (c.1963C>T) is classified Likely pathogenic in TP63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2021-12-21). No allele count reported in gnomAD v4.1 (AN 1,614,050); Associated with limb-mammary syndrome.

What condition is associated with TP63 p.Arg655Ter (c.1963C>T)?

TP63 p.Arg655Ter (c.1963C>T) is associated with limb-mammary syndrome (ClinVar).

How common is TP63 p.Arg655Ter (c.1963C>T) in the general population?

TP63 p.Arg655Ter (c.1963C>T) is no allele count reported in gnomAD v4.1 (AN 1,614,050) (gnomAD).

TP63 p.Arg655Ter

c.1963C>T · rs760967074 · VCV2434205

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,050)

Conditions

limb-mammary syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 2.8, phastCons 0.99
Overall
CADD	42.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,614,050). 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.Arg655Ter
Coding: c.1963C>T
MANE Select: NM_003722
dbSNP: rs760967074
Type: single nucleotide variant
Location: chr3:189894422 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB
Residue 655: 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); a UniProt-annotated variant site (in lms); a UniProt-annotated variant site (in pof21; results in increased transcriptional activation in luciferase reporter assays); the 'transactivation inhibition' region

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 p.Arg655Gln Uncertain significance ★ same residue
TP63 p.Arg243Trp Pathogenic ★★ same condition
TP63 p.Arg343Gln Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Arg21His Uncertain significance ★★ ⚠ same condition
TP63 p.Arg37Gln Uncertain significance ★★ ⚠ same condition
TP63 p.Arg674His Uncertain significance ★★ same condition
TP63 p.Arg7Trp Uncertain significance ★★ ⚠ same condition
TP63 p.Arg97Cys 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-arg655ter (accessed [today's date]).

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