Is PCK2 p.Pro124= (c.372T>C) pathogenic?

PCK2 p.Pro124= (c.372T>C) is classified Benign in PCK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-29). Common (popmax 19.5%, eas) — too common for a highly-penetrant pathogenic allele.

PCK2 p.Pro124=

Q: How common is PCK2 p.Pro124= (c.372T>C) in the general population?

PCK2 p.Pro124= (c.372T>C) is common (popmax 19.5%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.372T>C · rs2229661 · VCV559131

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 19.5%, 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 0.15	GERP 0.85, phastCons 0.99
Overall
CADD	7.909	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 19.5% East Asian · 8,748/44,858 alleles

Filtering AF 19.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 19%

Overall 1.34% 21,600/1,614,018 alleles · common exomes 17,119/1,461,776 · genomes 4,481/152,242 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	19.5%	5
African / African-American	6.4%	16
South Asian	3.08%	32
Finnishnot grpmax-eligible	2.35%	43
Admixed American	2.27%	44
Middle Eastern	2.01%	50
Remaining individualsnot grpmax-eligible	1.75%	57
Ashkenazi Jewishnot grpmax-eligible	0.669%	150
European (non-Finnish)	0.0823%	1,215

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: PCK2
Protein: p.Pro124=
Coding: c.372T>C
MANE Select: NM_004563
dbSNP: rs2229661
Type: single nucleotide variant
Location: chr14:24098299 (GRCh38)

Full PCK2 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/pck2-p-pro124 (accessed [today's date]).

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