Is TP53 p.Thr155Ala (c.463A>G) pathogenic?

TP53 p.Thr155Ala (c.463A>G) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-08). AlphaMissense: likely benign (0.086); Very rare (popmax 0.004%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Thr155Ala (c.463A>G)?

TP53 p.Thr155Ala (c.463A>G) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Thr155Ala (c.463A>G) in the general population?

TP53 p.Thr155Ala (c.463A>G) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about TP53 p.Thr155Ala (c.463A>G)?

AlphaMissense predicts likely benign (score 0.086) — an in-silico prediction, not a clinical call.

TP53 p.Thr155Ala

c.463A>G · rs772683278 · VCV458544

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.086 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.086	likely benign
REVEL	0.337	indeterminate
SaProt	LLR -6.45	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.2	GERP -2.3
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	5.897	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

Grpmax group 0.004% African / African-American · 3/75,000 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,614,044 alleles · very rare exomes 4/1,461,880 · genomes 0/152,164 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,000
South Asian	0.0011%	91,074

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: TP53
Protein: p.Thr155Ala
Coding: c.463A>G
MANE Select: NM_000546
dbSNP: rs772683278
Type: single nucleotide variant
Location: chr17:7675149 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 155: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation; does not induce snai1 degradation); the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; the 'required for interaction with fbxo42' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Thr155Asn Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Thr155= Benign/Likely benign ★★ same residue
TP53 p.Thr155Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Thr155Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Thr155Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Thr155_Ala159del Pathogenic ★ same residue
TP53 p.Thr155_Arg156del Pathogenic ★ same residue
TP53 p.Thr155fs Pathogenic ★ same residue

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-thr155ala (accessed [today's date]).

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