Is PCK2 p.Pro87Arg (c.260C>G) pathogenic?

PCK2 p.Pro87Arg (c.260C>G) is classified Uncertain significance in PCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-09-16). AlphaMissense: likely benign (0.0821); Very rare (popmax 0.00267%, afr).

How common is PCK2 p.Pro87Arg (c.260C>G) in the general population?

PCK2 p.Pro87Arg (c.260C>G) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about PCK2 p.Pro87Arg (c.260C>G)?

AlphaMissense predicts likely benign (score 0.0821) — an in-silico prediction, not a clinical call.

PCK2 p.Pro87Arg

c.260C>G · rs1363281259 · VCV618264

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0821 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0821	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -6.20	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 9,555 bp · p 0.49 · regional, not allelic
Overall
CADD	17.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,880 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,736 alleles · very rare exomes 1/1,461,678 · genomes 1/152,058 · joint denominator

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.Pro87Arg
Coding: c.260C>G
MANE Select: NM_004563
dbSNP: rs1363281259
Type: single nucleotide variant
Location: chr14:24097122 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.04
Residue 87: a UniProt-annotated variant site (found in a patient with abnormal gait and demyelinating peripheral neuropathy; uncertain significance)

Full PCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PCK2 p.Arg189Cys Uncertain significance ★★ ⚠ same type
PCK2 p.Asn91Lys Uncertain significance ★★ same type
PCK2 p.Leu582Ser Uncertain significance ★★ ⚠ same type
PCK2 p.Ser612Arg Uncertain significance ★★ ⚠ same type
PCK2 p.Arg561Gln Benign ★★ ⚠ same type
PCK2 p.Gly406Ser Benign ★★ ⚠ same type
PCK2 p.Lys295= Benign/Likely benign ★★ same type
PCK2 c.1234+1G>T Conflicting classifications of pathogenicity ★ same type

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-pro87arg (accessed [today's date]).

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