Is TP53RK p.Ala4= (c.12C>T) pathogenic?

TP53RK p.Ala4= (c.12C>T) is classified Benign in TP53RK (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Common (popmax 28.8%, eas) — too common for a highly-penetrant pathogenic allele.

TP53RK p.Ala4=

Q: How common is TP53RK p.Ala4= (c.12C>T) in the general population?

TP53RK p.Ala4= (c.12C>T) is common (popmax 28.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.12C>T · rs2664523 · VCV1230926

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 28.8%, eas) — too common for a highly-penetrant pathogenic allele

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -5.9	GERP -2.9
Overall
CADD	1.966	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.8% East Asian · 12,249/42,468 alleles

Filtering AF 28.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.2%

Overall 9.31% 144,859/1,555,824 alleles · common exomes 127,755/1,403,544 · genomes 17,104/152,280 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	28.8%	3
Admixed American	21%	5
South Asian	16.1%	6
African / African-American	13.3%	7
Middle Eastern	12.3%	8
Finnishnot grpmax-eligible	11.2%	9
Remaining individualsnot grpmax-eligible	10.5%	10
European (non-Finnish)	7.23%	14
Ashkenazi Jewishnot grpmax-eligible	6.83%	15
Amishnot grpmax-eligible	4.28%	23

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.Ala4=
Coding: c.12C>T
MANE Select: NM_033550
dbSNP: rs2664523
Type: single nucleotide variant
Location: chr20:46689403 (GRCh38)

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

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-ala4 (accessed [today's date]).

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