Is TP53 p.Leu383= (c.1149C>T) pathogenic?

TP53 p.Leu383= (c.1149C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-01-26). Very rare (popmax 0.00669%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Leu383= (c.1149C>T)?

TP53 p.Leu383= (c.1149C>T) is associated with hereditary neoplastic syndrome, colon carcinoma, head and neck squamous cell carcinoma (ClinVar).

How common is TP53 p.Leu383= (c.1149C>T) in the general population?

TP53 p.Leu383= (c.1149C>T) is very rare (popmax 0.00669%, nfe) (gnomAD).

TP53 p.Leu383=

c.1149C>T · rs373710656 · VCV183740

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00669%, nfe)

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 -2.6	GERP -4.6
Overall
CADD	0.154	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% European (non-Finnish) · 79/1,180,024 alleles

Filtering AF 0.00546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00533% 86/1,614,060 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00669%	14,937
Admixed American	0.005%	19,998
Remaining individualsnot grpmax-eligible	0.0048%	20,830
African / African-American	0.00133%	74,934

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.Leu383=
Coding: c.1149C>T
MANE Select: NM_000546
dbSNP: rs373710656
Type: single nucleotide variant
Location: chr17:7669642 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 383: the 'interaction with carm1' region; an α-helix; the 'disordered' region; the 'basic (repression of dna-binding)' region; the 'interaction with morn3' 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: colon carcinoma head and neck squamous cell carcinoma Li-Fraumeni syndrome

Similar variants

TP53 p.Leu383Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
TP53 p.Leu383Pro Uncertain significance ★ ⚠ same residue
TP53 p.Leu383fs 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
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-leu383 (accessed [today's date]).

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