Is TP53 p.Gln192Pro (c.575A>C) pathogenic?

TP53 p.Gln192Pro (c.575A>C) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-19). AlphaMissense: likely benign (0.3204); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Gln192Pro (c.575A>C)?

TP53 p.Gln192Pro (c.575A>C) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Gln192Pro (c.575A>C) in the general population?

TP53 p.Gln192Pro (c.575A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Gln192Pro (c.575A>C)?

AlphaMissense predicts likely benign (score 0.3204) — an in-silico prediction, not a clinical call.

TP53 p.Gln192Pro

c.575A>C · rs730882002 · VCV1036209

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3204 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.3204	likely benign
REVEL	0.769	pathogenic-leaning
SaProt	LLR -10.41	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	Δ0.31	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	25.3	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.Gln192Pro
Coding: c.575A>C
MANE Select: NM_000546
dbSNP: rs730882002
Type: single nucleotide variant
Location: chr17:7674956 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 192: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (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

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

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Gln192Ter Pathogenic ★★ same residue
TP53 p.Gln192Glu Uncertain significance ★★ ⚠ same residue
TP53 p.Gln192His Uncertain significance ★★ same residue
TP53 p.Gln192= Benign/Likely benign ★★ same residue
TP53 p.Gln192Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Gln192_His193del Pathogenic ★ same residue
TP53 p.Gln192_Leu194del Likely pathogenic ★ same residue
TP53 p.Gln192fs 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-gln192pro (accessed [today's date]).

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