Is TP53 p.Ala83= (c.249G>A) pathogenic?

TP53 p.Ala83= (c.249G>A) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-20). Very rare (popmax 0.00834%, amr); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ala83= (c.249G>A)?

TP53 p.Ala83= (c.249G>A) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Ala83= (c.249G>A) in the general population?

TP53 p.Ala83= (c.249G>A) is very rare (popmax 0.00834%, amr) (gnomAD).

TP53 p.Ala83=

c.249G>A · rs55754907 · VCV186003

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

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 -2.2	GERP -3.8
Overall
CADD	4.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,980 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00171% 25/1,460,886 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,996
Remaining individualsnot grpmax-eligible	0.0032%	31,207
East Asian	0.00223%	44,870
European (non-Finnish)	0.00144%	69,407

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.Ala83=
Coding: c.249G>A
MANE Select: NM_000546
dbSNP: rs55754907
Type: single nucleotide variant
Location: chr17:7676120 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 83: a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; somatic mutation); the 'interaction with ccar2' region; the 'interaction with hrmt1l2' 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

Also linked: Li-Fraumeni syndrome

Similar variants

TP53 p.Ala83Val Benign/Likely benign ★★ same residue
TP53 p.Ala83Glu Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Ala83Thr Uncertain significance ★ ⚠ same residue
TP53 p.Ala83Pro Likely benign ★ same residue
TP53 p.Ala83Ser 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-ala83 (accessed [today's date]).

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