Is CCPG1 p.Arg752Cys (c.2254C>T) pathogenic?

CCPG1 p.Arg752Cys (c.2254C>T) is classified Uncertain significance in CCPG1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-22). Very rare (popmax 0.000524%, nfe).

How common is CCPG1 p.Arg752Cys (c.2254C>T) in the general population?

CCPG1 p.Arg752Cys (c.2254C>T) is very rare (popmax 0.000524%, nfe) (gnomAD).

CCPG1 p.Arg752Cys

c.2254C>T · VCV3829190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000524%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
REVEL	0.047	moderately benign-leaning
Splicing
SpliceAI	Δ0.40	acceptor loss · deltas
Constraint at this position
Conservation	phyloP 8.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 3,524 bp · p 0.009 · regional, not allelic
Overall
CADD	27.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000524% European (non-Finnish) · 6/1,145,618 alleles

Filtering AF 0.000188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000124%

Overall 0.000435% 6/1,378,896 alleles · very rare

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: CCPG1
Protein: p.Arg752Cys
Coding: c.2254C>T
MANE Select: NM_001204450
Type: single nucleotide variant
Location: chr15:55356390 (GRCh38)
Gene constraint: LOEUF 0.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 62.96 · 1 PDB

Full CCPG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PIGB p.Ile537Met Pathogenic/Likely pathogenic ★★ ⚠ same type
PIGB p.Lys551Thr Benign ★★ same type
PIGB p.Ser509= Benign ★★ same type
CCPG1 p.Ala576Val Uncertain significance ★ ⚠ same type
CCPG1 p.Ala75Thr Uncertain significance ★ ⚠ same type
CCPG1 p.Arg179His Uncertain significance ★ ⚠ same type
CCPG1 p.Arg193Gln Uncertain significance ★ ⚠ same type
CCPG1 p.Arg193Trp Uncertain significance ★ ⚠ 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/ccpg1-p-arg752cys (accessed [today's date]).

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