Is TP53 p.Ala86= (c.258A>G) pathogenic?

TP53 p.Ala86= (c.258A>G) is classified Likely benign in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-19). Very rare (popmax 0.00223%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ala86= (c.258A>G)?

TP53 p.Ala86= (c.258A>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is TP53 p.Ala86= (c.258A>G) in the general population?

TP53 p.Ala86= (c.258A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

TP53 p.Ala86=

c.258A>G · rs1445371843 · VCV1793473

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

hereditary neoplastic syndrome

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 -1.6	GERP -4.4
Overall
CADD	2.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,858 alleles

Overall 6.2e-05% 1/1,612,818 alleles · very rare exomes 1/1,460,720 · genomes 0/152,098 · joint denominator

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.Ala86=
Coding: c.258A>G
MANE Select: NM_000546
dbSNP: rs1445371843
Type: single nucleotide variant
Location: chr17:7676111 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 86: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); the 'interaction with ccar2' region; the 'disordered' region; the 'interaction with wwox' 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.Ala86Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala86Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala86Val Conflicting classifications of pathogenicity ★ ⚠ 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
TP53 p.Ala138Pro Likely pathogenic ★★★ same condition
TP53 p.Ala138Val Likely 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-ala86 (accessed [today's date]).

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