Is TP53 p.Ser185Ile (c.554_555delinsTT) pathogenic?

TP53 p.Ser185Ile (c.554555delinsTT) is classified Uncertain significance in TP53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-30). Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ser185Ile (c.554_555delinsTT)?

TP53 p.Ser185Ile (c.554_555delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

TP53 p.Ser185Ile

c.554_555delinsTT · VCV4759033

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

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 · substitutions only
Constraint at this position
Conservation	phyloP -2.7	GERP -5.1
Regional constraint	o/e 0.89	unconstrained · MANE · 6,982 bp · p 0.0085 · regional, not allelic

Variant & gene context

Gene: TP53
Protein: p.Ser185Ile
Coding: c.554_555delinsTT
MANE Select: NM_000546
Type: Indel
Location: chr17:7675057 (GRCh38)
Gene constraint: LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 75.83 · 321 PDB
Residue 185: a DNA-binding region; the 'interaction with axin1' region; the 'interaction with ccar2' region; a UniProt-annotated variant site (in a sporadic cancer; somatic mutation); a UniProt-annotated variant site (in sporadic cancers; 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.Ser185Asn Likely benign ★★★ same residue
TP53 p.Ser185= Benign/Likely benign ★★ same residue
TP53 p.Ser185Arg Likely benign ★ ⚠ same residue
TP53 p.Pro72Cys Uncertain significance ★★★ same condition
TP53 p.Arg213Trp Pathogenic/Likely pathogenic ★★ same condition
TP53 p.Pro72Ser Uncertain significance ★★ same condition
TP53 c.96+15_96+31delinsC Likely benign ★★ same condition
TP53 c.559+2_559+3delinsGT 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-ser185ile (accessed [today's date]).

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