Is PCK2 p.Pro427= (c.1281G>A) pathogenic?

PCK2 p.Pro427= (c.1281G>A) is classified Uncertain significance in PCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-18). Ultra-rare (popmax 0.0659%, sas).

How common is PCK2 p.Pro427= (c.1281G>A) in the general population?

PCK2 p.Pro427= (c.1281G>A) is ultra-rare (popmax 0.0659%, sas) (gnomAD).

PCK2 p.Pro427=

c.1281G>A · rs376631075 · VCV2901624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0659%, sas)

⚠ 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 0.47	GERP -5.9, phastCons 0.99
Overall
CADD	17.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0659% South Asian · 60/91,076 alleles

Filtering AF 0.0525% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0476%

Overall 0.00459% 74/1,613,904 alleles · ultra-rare exomes 66/1,461,620 · genomes 8/152,284 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0659%	1,518
Middle Eastern	0.033%	3,026
African / African-American	0.00133%	75,030
European (non-Finnish)	0.000932%	107,255

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.Pro427=
Coding: c.1281G>A
MANE Select: NM_004563
dbSNP: rs376631075
Type: single nucleotide variant
Location: chr14:24102799 (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-pro427 (accessed [today's date]).

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