Is PCK2 p.Pro232Ser (c.694C>T) pathogenic?

PCK2 p.Pro232Ser (c.694C>T) is classified Uncertain significance in PCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-10). AlphaMissense: ambiguous (0.5146); Rare (popmax 0.128%, afr).

How common is PCK2 p.Pro232Ser (c.694C>T) in the general population?

PCK2 p.Pro232Ser (c.694C>T) is rare (popmax 0.128%, afr) (gnomAD).

What do computational predictors say about PCK2 p.Pro232Ser (c.694C>T)?

AlphaMissense predicts ambiguous (score 0.5146) — an in-silico prediction, not a clinical call.

PCK2 p.Pro232Ser

c.694C>T · rs144458057 · VCV3210242

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5146 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.128%, afr)

⚠ 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
AlphaMissense	0.5146	ambiguous
REVEL	0.456	indeterminate
SaProt	LLR -9.42	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 9,555 bp · p 0.49 · regional, not allelic
Overall
CADD	24.5	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

Grpmax group 0.128% African / African-American · 96/74,796 alleles

Filtering AF 0.108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0998%

Overall 0.0069% 111/1,608,176 alleles · rare exomes 60/1,456,234 · genomes 51/151,942 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.128%	779
Middle Eastern	0.0165%	6,068
Remaining individualsnot grpmax-eligible	0.0129%	7,772
South Asian	0.00549%	18,202
Admixed American	0.00167%	59,902

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.Pro232Ser
Coding: c.694C>T
MANE Select: NM_004563
dbSNP: rs144458057
Type: single nucleotide variant
Location: chr14:24099078 (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-pro232ser (accessed [today's date]).

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