Is PCK2 p.Phe249= (c.747C>T) pathogenic?

PCK2 p.Phe249= (c.747C>T) is classified Benign/Likely benign in PCK2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-06-01). Rare (popmax 0.804%, eas).

How common is PCK2 p.Phe249= (c.747C>T) in the general population?

PCK2 p.Phe249= (c.747C>T) is rare (popmax 0.804%, eas) (gnomAD).

PCK2 p.Phe249=

c.747C>T · rs149974910 · VCV559137

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.804%, eas)

⚠ 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 1.8	GERP 0.65, phastCons 1
Overall
CADD	13.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.804% East Asian · 361/44,888 alleles

Filtering AF 0.736% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.709%

Overall 0.463% 7,469/1,612,296 alleles · rare exomes 6,758/1,459,912 · genomes 711/152,384 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	2.25%	44
East Asiangrpmax	0.804%	124
Remaining individualsnot grpmax-eligible	0.467%	214
European (non-Finnish)	0.441%	227
Ashkenazi Jewishnot grpmax-eligible	0.223%	449
Admixed American	0.08%	1,250
Middle Eastern	0.066%	1,516
South Asian	0.0604%	1,656
African / African-American	0.0546%	1,831

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe249=
Coding: c.747C>T
MANE Select: NM_004563
dbSNP: rs149974910
Type: single nucleotide variant
Location: chr14:24099131 (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-phe249 (accessed [today's date]).

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