Is TP53 p.Ala355Ser (c.1063G>T) pathogenic?

TP53 p.Ala355Ser (c.1063G>T) is classified Conflicting classifications of pathogenicity in TP53 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-04-06). AlphaMissense: likely benign (0.0786); Absent from gnomAD v4.1; Associated with hereditary breast carcinoma.

What condition is associated with TP53 p.Ala355Ser (c.1063G>T)?

TP53 p.Ala355Ser (c.1063G>T) is associated with hereditary breast carcinoma, hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Ala355Ser (c.1063G>T) in the general population?

TP53 p.Ala355Ser (c.1063G>T) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary breast cancer inherited?

Typically Autosomal dominant, Multigenic/multifactorial (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about TP53 p.Ala355Ser (c.1063G>T)?

AlphaMissense predicts likely benign (score 0.0786) — an in-silico prediction, not a clinical call.

TP53 p.Ala355Ser

c.1063G>T · rs1157427821 · VCV1468494

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0786 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary breast carcinoma

Computational evidence

Protein change
AlphaMissense	0.0786	likely benign
REVEL	0.212	benign-leaning
SaProt	LLR -6.02	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 -1.8	GERP -4
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	11.47	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.Ala355Ser
Coding: c.1063G>T
MANE Select: NM_000546
dbSNP: rs1157427821
Type: single nucleotide variant
Location: chr17:7670646 (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 breast carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome Li-Fraumeni syndrome

For Hereditary breast cancer (Orphanet):

Inheritance: Autosomal dominant, Multigenic/multifactorial
Onset: Adult, Elderly

Similar variants

TP53 p.Ala355Asp Uncertain significance ★★ ⚠ same residue
TP53 p.Ala355Gly 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-ala355ser (accessed [today's date]).

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