Is CIB2 p.Arg186= (c.558G>T) pathogenic?

CIB2 p.Arg186= (c.558G>T) is classified Likely benign in CIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Absent from gnomAD v4.1.

How common is CIB2 p.Arg186= (c.558G>T) in the general population?

CIB2 p.Arg186= (c.558G>T) is absent from gnomAD v4.1 (gnomAD).

CIB2 p.Arg186=

c.558G>T · rs1567047205 · VCV2645608

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.23	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.23	GERP -3.7, phastCons 0.98
Overall
CADD	11.26	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: CIB2
Protein: p.Arg186=
Coding: c.558G>T
MANE Select: NM_006383
dbSNP: rs1567047205
Type: single nucleotide variant
Location: chr15:78105317 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 186: a UniProt-annotated variant site (in dfnb48); a UniProt-annotated variant site (in dfnb48; uncertain significance); a UniProt-annotated variant site (in dfnb48; inhibits the ability to decrease atp-induced calcium release; decreases interaction with tmc1 and tmc2; does not affect the localization in the cuticular plate or to the tip of stereocilia; does not affect binding with whrn)

Full CIB2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB2 p.Arg186Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
CIB2 p.Arg186Trp Conflicting classifications of pathogenicity ★ ⚠ same residue
CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same type
CIB2 p.Arg33Ter Pathogenic ★★ same type
CIB2 p.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
CIB2 c.198+3A>G Uncertain significance ★★ same type
CIB2 p.Ala108Thr Uncertain significance ★★ ⚠ same type
CIB2 p.Ala76Val 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/cib2-p-arg186 (accessed [today's date]).

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