Is TP53 p.His296Arg (c.887A>G) pathogenic?

TP53 p.His296Arg (c.887A>G) is classified Likely pathogenic in TP53 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely benign (0.0587); Absent from gnomAD v4.1.

How common is TP53 p.His296Arg (c.887A>G) in the general population?

TP53 p.His296Arg (c.887A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.His296Arg (c.887A>G)?

AlphaMissense predicts likely benign (score 0.0587) — an in-silico prediction, not a clinical call.

TP53 p.His296Arg

c.887A>G · rs483352696 · VCV100816

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0587 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0587	likely benign ⚠ discordant with ClinVar
REVEL	0.328	indeterminate
SaProt	LLR -5.70	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP -0.97, phastCons 0.13
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	4.621	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: TP53
Protein: p.His296Arg
Coding: c.887A>G
MANE Select: NM_000546
dbSNP: rs483352696
Type: single nucleotide variant
Location: chr17:7673733 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 296: a UniProt-annotated variant site (in sporadic cancers; somatic mutation; requires 2 nucleotide substitutions); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'disordered' region; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region

Full TP53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TP53 p.His296Tyr Likely benign ★★★ same residue
TP53 p.His296= Likely benign ★ same residue
TP53 p.His296fs Pathogenic ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same type
TP53 c.919+1G>A Pathogenic ★★★ same type
TP53 c.97-1G>A Pathogenic ★★★ same type
TP53 p.Ala138Pro Likely pathogenic ★★★ same type
TP53 p.Ala138Val Likely pathogenic ★★★ same type

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/tp53-p-his296arg (accessed [today's date]).

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