Is TP73 p.Pro486Leu (c.1457C>T) pathogenic?

TP73 p.Pro486Leu (c.1457C>T) is classified Uncertain significance in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.1166); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TP73 p.Pro486Leu (c.1457C>T)?

TP73 p.Pro486Leu (c.1457C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TP73 p.Pro486Leu (c.1457C>T) in the general population?

TP73 p.Pro486Leu (c.1457C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP73 p.Pro486Leu (c.1457C>T)?

AlphaMissense predicts likely benign (score 0.1166) — an in-silico prediction, not a clinical call.

TP73 p.Pro486Leu

c.1457C>T · VCV3460407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1166 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1166	likely benign
REVEL	0.687	pathogenic-leaning
SaProt	LLR -7.74	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 0.95
Regional constraint	o/e 0.87	unconstrained · MANE · 5,880 bp · p 0.0021 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP73
Protein: p.Pro486Leu
Coding: c.1457C>T
MANE Select: NM_005427
Type: single nucleotide variant
Location: chr1:3731038 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 486: the sam domain; a UniProt-annotated variant site (in cild47)

Full TP73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP73 p.Pro486Arg Uncertain significance ★ ⚠ same residue
TP73 p.Gly451Arg Uncertain significance ★★ ⚠ same condition
TP73 p.Ala100Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala112Val Uncertain significance ★ ⚠ same condition
TP73 p.Ala156Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala320Thr Uncertain significance ★ ⚠ same condition
TP73 p.Ala441Pro Uncertain significance ★ ⚠ same condition
TP73 p.Ala441Thr 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/tp73-p-pro486leu (accessed [today's date]).

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