Is TP53 p.Ala129= (c.387C>T) pathogenic?

TP53 p.Ala129= (c.387C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-04-02). Very rare (popmax 0.00223%, eas); Associated with Li-Fraumeni syndrome 1.

What condition is associated with TP53 p.Ala129= (c.387C>T)?

TP53 p.Ala129= (c.387C>T) is associated with Li-Fraumeni syndrome 1, prostate cancer, hereditary, 1, hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Ala129= (c.387C>T) in the general population?

TP53 p.Ala129= (c.387C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

TP53 p.Ala129=

c.387C>T · rs2543607814 · VCV1735782

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

Li-Fraumeni syndrome 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.9, phastCons 0.62
Overall
CADD	8.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,874 alleles

Overall 0.000124% 2/1,613,990 alleles · very rare exomes 2/1,461,738 · genomes 0/152,252 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,874
European (non-Finnish)	8.48e-05%	1,179,924

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: TP53
Protein: p.Ala129=
Coding: c.387C>T
MANE Select: NM_000546
dbSNP: rs2543607814
Type: single nucleotide variant
Location: chr17:7675225 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 129: a DNA-binding region; the 'interaction with axin1' region; a turn; the 'interaction with ccar2' region; a UniProt-annotated variant site (in sporadic cancers; somatic mutation); a UniProt-annotated variant site (in a sporadic cancer; 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

Li-Fraumeni syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: prostate cancer, hereditary, 1 hereditary neoplastic syndrome Li-Fraumeni syndrome

Similar variants

TP53 p.Ala129Gly Uncertain significance ★ ⚠ same residue
TP53 p.Ala129Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala129Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala129Asp Benign ★ same residue
TP53 p.Ala129_Leu130insProAla Uncertain significance ★ same residue
TP53 p.Ala129fs Uncertain significance 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-ala129 (accessed [today's date]).

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