Is TP53 p.Ala355Asp (c.1064C>A) pathogenic?

TP53 p.Ala355Asp (c.1064C>A) is classified Uncertain significance in TP53 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-07-11). AlphaMissense: likely benign (0.1078); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ala355Asp (c.1064C>A)?

TP53 p.Ala355Asp (c.1064C>A) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Ala355Asp (c.1064C>A) in the general population?

TP53 p.Ala355Asp (c.1064C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Ala355Asp (c.1064C>A)?

AlphaMissense predicts likely benign (score 0.1078) — an in-silico prediction, not a clinical call.

TP53 p.Ala355Asp

c.1064C>A · rs1555524382 · VCV2774647

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1078 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1078	likely benign
REVEL	0.21	benign-leaning
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.3
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	15.35	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.Ala355Asp
Coding: c.1064C>A
MANE Select: NM_000546
dbSNP: rs1555524382
Type: single nucleotide variant
Location: chr17:7670645 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 355: the 'interaction with carm1' region; a turn; the 'interaction with hipk2' region; the 'oligomerization' region; the 'disordered' region; the 'interaction with hipk1' 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.Ala355Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355Val Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala355fs Uncertain significance ★ same residue
TP53 p.Ala355= Likely benign ★ 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-ala355asp (accessed [today's date]).

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