Is TP53 p.Ser185= (c.555C>T) pathogenic?

TP53 p.Ser185= (c.555C>T) is classified Benign/Likely benign in TP53 (ClinVar, Multiple submitters, 12 submitters; last evaluated 2026-02-02). Very rare (popmax 0.00267%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with TP53 p.Ser185= (c.555C>T)?

TP53 p.Ser185= (c.555C>T) is associated with hereditary neoplastic syndrome, hereditary breast ovarian cancer syndrome, head and neck squamous cell carcinoma (ClinVar).

How common is TP53 p.Ser185= (c.555C>T) in the general population?

TP53 p.Ser185= (c.555C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

TP53 p.Ser185=

c.555C>T · rs367560109 · VCV184650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -5.1
Overall
CADD	0.355	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,934 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000743% 12/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,467
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.000763%	131,108

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.Ser185=
Coding: c.555C>T
MANE Select: NM_000546
dbSNP: rs367560109
Type: single nucleotide variant
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

Also linked: hereditary breast ovarian cancer syndrome head and neck squamous cell carcinoma Li-Fraumeni syndrome

Similar variants

TP53 p.Ser185Asn Likely benign ★★★ same residue
TP53 p.Ser185Arg Likely benign ★ ⚠ same residue
TP53 p.Ser185Ile 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-ser185 (accessed [today's date]).

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