Is TP53RK p.Ala71Pro (c.211G>C) pathogenic?

TP53RK p.Ala71Pro (c.211G>C) is classified Uncertain significance in TP53RK (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-08). AlphaMissense: ambiguous (0.5272); Absent from gnomAD v4.1.

How common is TP53RK p.Ala71Pro (c.211G>C) in the general population?

TP53RK p.Ala71Pro (c.211G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TP53RK p.Ala71Pro (c.211G>C)?

AlphaMissense predicts ambiguous (score 0.5272) — an in-silico prediction, not a clinical call.

TP53RK p.Ala71Pro

c.211G>C · VCV4689522

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5272 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5272	ambiguous
REVEL	0.05	moderately benign-leaning
SaProt	LLR -13.59	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.91	GERP 0.58, phastCons 0.99
Regional constraint	o/e 1.03	unconstrained · MANE · 2,658 bp · p 0.55 · regional, not allelic
Overall
CADD	20.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TP53RK
Protein: p.Ala71Pro
Coding: c.211G>C
MANE Select: NM_033550
Type: single nucleotide variant
Location: chr20:46689204 (GRCh38)
Gene constraint: LOEUF 1.776 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.58 · 6 PDB
Residue 71: the protein kinase domain; an α-helix

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

Similar variants

TP53RK p.Ala71Gly Uncertain significance ★ ⚠ same residue
TPRKB p.Lys71Arg 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

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-ala71pro (accessed [today's date]).

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