Is TP73 p.His488= (c.1464C>T) pathogenic?

TP73 p.His488= (c.1464C>T) is classified Likely benign in TP73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). Ultra-rare (popmax 0.0154%, sas); Associated with Inborn genetic diseases.

What condition is associated with TP73 p.His488= (c.1464C>T)?

TP73 p.His488= (c.1464C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TP73 p.His488= (c.1464C>T) in the general population?

TP73 p.His488= (c.1464C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

TP73 p.His488=

c.1464C>T · VCV3972531

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.407	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -3.8
Overall
CADD	6.903	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/91,044 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.00416% 67/1,612,026 alleles · ultra-rare exomes 60/1,459,684 · genomes 7/152,342 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0511%	1,956
South Asiangrpmax	0.0154%	6,503
East Asian	0.00446%	22,431
African / African-American	0.00267%	37,523
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,444
European (non-Finnish)	0.00127%	78,636

Finnish 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: TP73
Protein: p.His488=
Coding: c.1464C>T
MANE Select: NM_005427
Type: single nucleotide variant
Location: chr1:3731045 (GRCh38)
Gene constraint: LOEUF 0.576 · pLI 0.29 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 66.25 · 28 PDB
Residue 488: 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.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-his488 (accessed [today's date]).

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