TP53 p.Asp186=
c.558T>C · rs375275361 · VCV184048
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 8 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00186%, nfe)
Conditions
2
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 -1.3 | GERP -4.8 |
| Overall | ||
| CADD | 1.056 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00186%
European (non-Finnish) · 22/1,180,002 alleles
Filtering AF
0.00122%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00104%
Overall
0.00149%
24/1,614,156 alleles · very rare
exomes 21/1,461,852 · genomes 3/152,304 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00186% | 53,637 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| African / African-American | 0.00133% | 75,048 |
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.Asp186=
- Coding
- c.558T>C
- MANE Select
- NM_000546
- dbSNP
- rs375275361
- Type
- single nucleotide variant
- Location
- chr17:7675054 (GRCh38)
- Gene constraint
- LOEUF 0.449 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.83 · 321 PDB
- Residue 186
- 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
Similar variants
- TP53 p.Asp186Asn Likely benign ★★★ same residue
- TP53 p.Asp186Glu Likely benign ★★ 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
- TP53 p.Ala347Asp 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-asp186 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown