Is TP53 p.Ala83Val (c.248C>T) pathogenic?

TP53 p.Ala83Val (c.248C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-04-29). AlphaMissense: likely benign (0.0854); Rare (popmax 0.15%, mid); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ala83Val (c.248C>T)?

TP53 p.Ala83Val (c.248C>T) is associated with hereditary neoplastic syndrome, Li-Fraumeni syndrome (ClinVar).

How common is TP53 p.Ala83Val (c.248C>T) in the general population?

TP53 p.Ala83Val (c.248C>T) is rare (popmax 0.15%, mid) (gnomAD).

What do computational predictors say about TP53 p.Ala83Val (c.248C>T)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

TP53 p.Ala83Val

c.248C>T · rs201717599 · VCV127805

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.15%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.377	indeterminate
SaProt	LLR -7.81	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.46	GERP -3.8
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic
Overall
CADD	8.373	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

Grpmax group 0.15% Middle Eastern · 8/5,332 alleles

Filtering AF 0.0746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0545%

Overall 0.00626% 101/1,613,120 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.15%	666
South Asian	0.0626%	1,597
Admixed American	0.0167%	5,999
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869
African / African-American	0.00933%	10,714
Remaining individualsnot grpmax-eligible	0.00481%	20,805
East Asian	0.00223%	44,866
European (non-Finnish)	0.00102%	98,328

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.Ala83Val
Coding: c.248C>T
MANE Select: NM_000546
dbSNP: rs201717599
Type: single nucleotide variant
Location: chr17:7676121 (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.Ala83= 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-ala83val (accessed [today's date]).

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