Is TP63 p.Ser530= (c.1590C>T) pathogenic?

TP63 p.Ser530= (c.1590C>T) is classified Likely benign in TP63 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-01). Very rare (popmax 0.00212%, nfe); Associated with TP63-Related Spectrum Disorders.

What condition is associated with TP63 p.Ser530= (c.1590C>T)?

TP63 p.Ser530= (c.1590C>T) is associated with TP63-Related Spectrum Disorders (ClinVar).

How common is TP63 p.Ser530= (c.1590C>T) in the general population?

TP63 p.Ser530= (c.1590C>T) is very rare (popmax 0.00212%, nfe) (gnomAD).

TP63 p.Ser530=

c.1590C>T · rs373284695 · VCV1463038

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Conditions

TP63-Related Spectrum Disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Overall
CADD	13.28	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,180,014 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00192% 31/1,614,140 alleles · very rare exomes 31/1,461,816 · genomes 0/152,324 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)grpmax	0.00212%	47,201
South Asian	0.0011%	91,076

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: TP63
Protein: p.Ser530=
Coding: c.1590C>T
MANE Select: NM_003722
dbSNP: rs373284695
Type: single nucleotide variant
Location: chr3:189889422 (GRCh38)
Gene constraint: LOEUF 0.296 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 63.70 · 26 PDB

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

Disease context

TP63-Related Spectrum Disorders

Similar variants

TP63 p.Arg318His Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Cys561Tyr Likely pathogenic ★★ same condition
TP63 p.Gly173Arg Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Gly173Asp Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Gly336Asp Pathogenic/Likely pathogenic ★★ same condition
TP63 p.Gly557Val Pathogenic/Likely pathogenic ★★ same condition
TP63 p.His247Arg Pathogenic ★★ same condition
TP63 p.His247Tyr 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/tp63-p-ser530 (accessed [today's date]).

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