Is TP73 p.His458= (c.1374C>T) pathogenic?

TP73 p.His458= (c.1374C>T) is classified Likely benign in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). Rare (popmax 0.116%, mid); Associated with Inborn genetic diseases.

What condition is associated with TP73 p.His458= (c.1374C>T)?

TP73 p.His458= (c.1374C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TP73 p.His458= (c.1374C>T) in the general population?

TP73 p.His458= (c.1374C>T) is rare (popmax 0.116%, mid) (gnomAD).

TP73 p.His458=

c.1374C>T · VCV3328241

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.116%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.311	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -3.4
Overall
CADD	2.037	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.116% Middle Eastern · 7/6,040 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0385%

Overall 0.0041% 66/1,610,556 alleles · rare exomes 60/1,458,380 · genomes 6/152,176 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.116%	863
African / African-American	0.0214%	4,679
South Asian	0.0154%	6,474
Remaining individualsnot grpmax-eligible	0.00802%	12,463
Admixed American	0.00501%	19,951
European (non-Finnish)	0.00178%	56,150

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: TP73
Protein: p.His458=
Coding: c.1374C>T
MANE Select: NM_005427
Type: single nucleotide variant
Location: chr1:3730955 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 458: 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.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
TP73 p.Ala459Val 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-his458 (accessed [today's date]).

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