Is TP53RK p.Pro99= (c.297A>G) pathogenic?

TP53RK p.Pro99= (c.297A>G) is classified Likely benign in TP53RK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-03). Very rare (popmax 0.00129%, nfe).

How common is TP53RK p.Pro99= (c.297A>G) in the general population?

TP53RK p.Pro99= (c.297A>G) is very rare (popmax 0.00129%, nfe) (gnomAD).

TP53RK p.Pro99=

c.297A>G · rs777191510 · VCV2986974

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00129%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.05	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.5
Overall
CADD	0.646	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00129% European (non-Finnish) · 15/1,163,738 alleles

Filtering AF 0.000774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000614%

Overall 0.000946% 15/1,586,174 alleles · very rare exomes 14/1,434,014 · genomes 1/152,160 · joint denominator

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: TP53RK
Protein: p.Pro99=
Coding: c.297A>G
MANE Select: NM_033550
dbSNP: rs777191510
Type: single nucleotide variant
Location: chr20:46687218 (GRCh38)
Gene constraint: LOEUF 1.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.58 · 6 PDB
Residue 99: the protein kinase domain

Full TP53RK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TPRKB p.Ser99Ala Uncertain significance ★ ⚠ same residue
TP53RK p.Arg243His Uncertain significance ★★ ⚠ same type
TP53RK p.Leu200Val Uncertain significance ★★ ⚠ same type
TP53RK p.Lys230Thr Uncertain significance ★★ ⚠ same type
TP53RK p.Val120Met Uncertain significance ★★ ⚠ same type
TPRKB p.Ala92Thr Uncertain significance ★★ same type
TPRKB p.Arg14Thr Uncertain significance ★★ ⚠ same type
TPRKB p.Asn88Ser Uncertain significance ★★ ⚠ same type

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/tp53rk-p-pro99 (accessed [today's date]).

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