Is PCK2 p.Ala2= (c.6C>T) pathogenic?

PCK2 p.Ala2= (c.6C>T) is classified Benign in PCK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.75%, nfe).

How common is PCK2 p.Ala2= (c.6C>T) in the general population?

PCK2 p.Ala2= (c.6C>T) is low-frequency (popmax 3.75%, nfe) (gnomAD).

PCK2 p.Ala2=

c.6C>T · rs77298044 · VCV559129

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.75%, nfe)

⚠ 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 0.094	GERP -1.9, phastCons 0.95
Overall
CADD	13.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.75% European (non-Finnish) · 43,416/1,157,178 alleles

Filtering AF 3.72% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.71%

Overall 3.13% 48,894/1,559,660 alleles · low-frequency exomes 45,530/1,407,318 · genomes 3,364/152,342 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	3.75%	27
Remaining individualsnot grpmax-eligible	2.57%	39
Finnishnot grpmax-eligible	2.35%	43
Middle Eastern	1.69%	59
South Asian	1.3%	77
Ashkenazi Jewishnot grpmax-eligible	1.23%	81
Admixed American	1.23%	82
Amishnot grpmax-eligible	1.1%	91
African / African-American	0.563%	178
East Asian	0.0146%	6,827

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.Ala2=
Coding: c.6C>T
MANE Select: NM_004563
dbSNP: rs77298044
Type: single nucleotide variant
Location: chr14:24094411 (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-ala2 (accessed [today's date]).

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