Is TP53 p.Asp148Val (c.443A>T) pathogenic?

TP53 p.Asp148Val (c.443A>T) is classified Uncertain significance in TP53 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-01). AlphaMissense: likely benign (0.1965); Absent from gnomAD v4.1; Associated with prostate cancer, hereditary, 1.

What condition is associated with TP53 p.Asp148Val (c.443A>T)?

TP53 p.Asp148Val (c.443A>T) is associated with prostate cancer, hereditary, 1 (ClinVar).

How common is TP53 p.Asp148Val (c.443A>T) in the general population?

TP53 p.Asp148Val (c.443A>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial prostate cancer inherited?

Typically Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TP53 p.Asp148Val (c.443A>T)?

AlphaMissense predicts likely benign (score 0.1965) — an in-silico prediction, not a clinical call.

TP53 p.Asp148Val

c.443A>T · rs1046611742 · VCV2687708

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1965 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

prostate cancer, hereditary, 1

Computational evidence

Protein change
AlphaMissense	0.1965	likely benign
REVEL	0.551	indeterminate
SaProt	LLR -9.29	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 -1.2	GERP -4.9
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	8.375	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Asp148Val
Coding: c.443A>T
MANE Select: NM_000546
dbSNP: rs1046611742
Type: single nucleotide variant
Location: chr17:7675169 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 148: 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

prostate cancer, hereditary, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial prostate cancer (Orphanet):

Inheritance: Not applicable
Onset: Adult
Prevalence: 1-9 / 100 000 (United States)

Similar variants

TP53 p.Asp148Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asp148Asn Uncertain significance ★ ⚠ same residue
TP53 p.Asp148Glu Uncertain significance ★ ⚠ same residue
TP53 p.Asp148Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala138Gly Uncertain significance ★★★ ⚠ same condition
TP53 p.Ala159Asp Pathogenic/Likely pathogenic ★★ same condition
TP53 p.Tyr126Ter Pathogenic ★★ same condition
TP53 p.Gln144Arg 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/tp53-p-asp148val (accessed [today's date]).

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