Is TP53 p.Asn239Asp (c.715A>G) pathogenic?

TP53 p.Asn239Asp (c.715A>G) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.9944); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Asn239Asp (c.715A>G)?

TP53 p.Asn239Asp (c.715A>G) is associated with hereditary neoplastic syndrome, breast cancer, adrenocortical carcinoma, hereditary (ClinVar).

How common is TP53 p.Asn239Asp (c.715A>G) in the general population?

TP53 p.Asn239Asp (c.715A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Asn239Asp (c.715A>G)?

AlphaMissense predicts likely pathogenic (score 0.9944) — an in-silico prediction, not a clinical call.

TP53 p.Asn239Asp

c.715A>G · rs876660807 · VCV234036

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.9944 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,902)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.9944	likely pathogenic · top 7% in TP53
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -14.58	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	25.8	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

No allele count reported in gnomAD v4.1 (AN 1,613,902). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: TP53
Protein: p.Asn239Asp
Coding: c.715A>G
MANE Select: NM_000546
dbSNP: rs876660807
Type: single nucleotide variant
Location: chr17:7674248 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 239: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; the 'interaction with hipk1' region; the 'required for interaction with znf385a' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; somatic mutation)

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: breast cancer adrenocortical carcinoma, hereditary Li-Fraumeni syndrome

Similar variants

TP53 p.Asn239Ser Pathogenic/Likely pathogenic ★★ same residue
TP53 p.Asn239= Benign/Likely benign ★★ same residue
TP53 p.Asn239Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asn239Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asn239Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Asn239dup Uncertain significance ★★ same residue
TP53 p.Asn239_Gly245del Likely pathogenic ★ same residue
TP53 p.Asn239_Ser241delinsThr 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-asn239asp (accessed [today's date]).

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