Is TP53 p.Arg156Cys (c.466C>T) pathogenic?

TP53 p.Arg156Cys (c.466C>T) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 15 submitters; last evaluated 2025-11-24). AlphaMissense: likely benign (0.1809); Very rare (popmax 0.00401%, afr); Associated with glioma susceptibility 1.

What condition is associated with TP53 p.Arg156Cys (c.466C>T)?

TP53 p.Arg156Cys (c.466C>T) is associated with glioma susceptibility 1, colon carcinoma, bone osteosarcoma (ClinVar).

How common is TP53 p.Arg156Cys (c.466C>T) in the general population?

TP53 p.Arg156Cys (c.466C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about TP53 p.Arg156Cys (c.466C>T)?

AlphaMissense predicts likely benign (score 0.1809) — an in-silico prediction, not a clinical call.

TP53 p.Arg156Cys

c.466C>T · rs563378859 · VCV127810

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.1809 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

glioma susceptibility 1

Computational evidence

Protein change
AlphaMissense	0.1809	likely benign
REVEL	0.493	indeterminate
SaProt	LLR -9.03	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 4.6	GERP -2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	18.52	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 0.00401% African / African-American · 3/74,906 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00118% 19/1,614,030 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,969
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00127%	78,670

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.Arg156Cys
Coding: c.466C>T
MANE Select: NM_000546
dbSNP: rs563378859
Type: single nucleotide variant
Location: chr17:7675146 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 156: a DNA-binding region; the 'interaction with axin1' region; a β-strand; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in lfs; germline mutation and in sporadic cancers; somatic mutation); 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

glioma susceptibility 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: colon carcinoma bone osteosarcoma exocrine pancreatic carcinoma colorectal cancer hepatocellular carcinoma adrenocortical carcinoma, hereditary choroid plexus papilloma basal cell carcinoma, susceptibility to, 7 familial pancreatic carcinoma hereditary neoplastic syndrome nasopharyngeal carcinoma hereditary breast carcinoma Li-Fraumeni syndrome bone marrow failure syndrome 5

Similar variants

TP53 p.Arg156His Uncertain significance ★★★ ⚠ same residue
TP53 p.Arg156Pro Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Arg156= Benign/Likely benign ★★ same residue
TP53 p.Arg156Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Arg156Ser Uncertain significance ★ ⚠ same residue
TP53 p.Arg156_Arg158del Pathogenic ★ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ 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/tp53-p-arg156cys (accessed [today's date]).

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