Is CIB2 p.Gln12Ter (c.34C>T) pathogenic?

CIB2 p.Gln12Ter (c.34C>T) is classified Likely pathogenic in CIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-09). Very rare (popmax 0.00112%, sas); Associated with autosomal recessive nonsyndromic hearing loss 48.

What condition is associated with CIB2 p.Gln12Ter (c.34C>T)?

CIB2 p.Gln12Ter (c.34C>T) is associated with autosomal recessive nonsyndromic hearing loss 48 (ClinVar).

How common is CIB2 p.Gln12Ter (c.34C>T) in the general population?

CIB2 p.Gln12Ter (c.34C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

CIB2 p.Gln12Ter

c.34C>T · VCV4796692

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

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	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.6, phastCons 1
Overall
CADD	49.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,194 alleles

Overall 6.95e-05% 1/1,438,812 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: CIB2
Protein: p.Gln12Ter
Coding: c.34C>T
MANE Select: NM_006383
Type: single nucleotide variant
Location: chr15:78131182 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 12: 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.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
CIB2 p.Arg66Gln Uncertain significance ★★ ⚠ same condition
CIB2 p.Asn118Asp Uncertain significance ★★ ⚠ same condition
CIB2 p.Val75Met Uncertain significance ★★ ⚠ same condition
CIB2 c.199-1G>A Likely pathogenic ★ same condition
CIB2 p.Phe91Ser Likely pathogenic ★ same condition
CIB2 p.Arg104Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
CIB2 p.Arg134Leu Conflicting classifications of pathogenicity ★ ⚠ 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-gln12ter (accessed [today's date]).

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