Is CIB2 p.Ser96fs (c.286del) pathogenic?

CIB2 p.Ser96fs (c.286del) is classified Pathogenic in CIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Associated with autosomal recessive nonsyndromic hearing loss 48.

What condition is associated with CIB2 p.Ser96fs (c.286del)?

CIB2 p.Ser96fs (c.286del) is associated with autosomal recessive nonsyndromic hearing loss 48 (ClinVar).

CIB2 p.Ser96fs

c.286del · VCV3601868

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autosomal recessive nonsyndromic hearing loss 48

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: CIB2
Protein: p.Ser96fs
Coding: c.286del
MANE Select: NM_006383
Type: Deletion
Location: chr15:78109295 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 96: the ef-hand 1 domain; a UniProt-annotated variant site (in dfnb48); an α-helix

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

Disease context

autosomal recessive nonsyndromic hearing loss 48 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIB2 p.Glu100fs Pathogenic/Likely pathogenic ★★ same condition
CIB2 p.Ser96= Likely benign ★★ same residue
CIB2 p.Asp178fs Pathogenic ★ same condition
CIB2 p.Ile59fs Pathogenic ★ same condition
CIB2 p.Lys125fs Pathogenic ★ same condition
CIB2 p.Pro177fs Pathogenic ★ same condition
CIB2 p.Asp159fs Pathogenic same condition
CIB2 p.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition

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-ser96fs (accessed [today's date]).

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