Is C2 p.Arg189= (c.567G>A) pathogenic?

C2 p.Arg189= (c.567G>A) is classified Likely benign in C2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-29). Absent from gnomAD v4.1.

How common is C2 p.Arg189= (c.567G>A) in the general population?

C2 p.Arg189= (c.567G>A) is absent from gnomAD v4.1 (gnomAD).

C2 p.Arg189=

c.567G>A · rs1454631594 · VCV2958806

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.275	benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.3	GERP -1.7, phastCons 0.017
Overall
CADD	4.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: C2
Protein: p.Arg189=
Coding: c.567G>A
MANE Select: NM_000063
dbSNP: rs1454631594
Type: single nucleotide variant
Location: chr6:31933734 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.61 · 14 PDB
Residue 189: the sushi 3 domain; a β-strand

Full C2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ZBTB12 p.Asp189Glu Uncertain significance ★ ⚠ same residue
C2 c.1902+5G>A Uncertain significance ★★ same type
C2 c.2029+5G>A Uncertain significance ★★ same type
C2 p.Ala363Thr Uncertain significance ★★ ⚠ same type
C2 p.Ala682Glu Uncertain significance ★★ ⚠ same type
C2 p.Arg124Gln Uncertain significance ★★ ⚠ same type
C2 p.Arg129His Uncertain significance ★★ same type
C2 p.Arg174Cys 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/c2-p-arg189 (accessed [today's date]).

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