Is TP53 p.Ala129Asp (c.386C>A) pathogenic?

TP53 p.Ala129Asp (c.386C>A) is classified Benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-10). AlphaMissense: likely benign (0.0679); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ala129Asp (c.386C>A)?

TP53 p.Ala129Asp (c.386C>A) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Ala129Asp (c.386C>A) in the general population?

TP53 p.Ala129Asp (c.386C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53 p.Ala129Asp (c.386C>A)?

AlphaMissense predicts likely benign (score 0.0679) — an in-silico prediction, not a clinical call.

TP53 p.Ala129Asp

c.386C>A · rs137852792 · VCV1735669

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0679 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0679	likely benign
REVEL	0.553	indeterminate
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.019	GERP -4.9
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	0.41	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.Ala129Asp
Coding: c.386C>A
MANE Select: NM_000546
dbSNP: rs137852792
Type: single nucleotide variant
Location: chr17:7675226 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TP53 p.Ala129= Benign/Likely benign ★★ same residue
TP53 p.Ala129Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala129Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala129_Leu130insProAla Uncertain significance ★ same residue
TP53 p.Ala129Gly Uncertain significance ★ ⚠ same residue
TP53 c.375+5G>A Likely pathogenic ★★★ same condition
TP53 c.919+1G>A Pathogenic ★★★ same condition
TP53 c.97-1G>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-ala129asp (accessed [today's date]).

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