Is CIB2 p.Arg33Ter (c.97C>T) pathogenic?

CIB2 p.Arg33Ter (c.97C>T) is classified Pathogenic in CIB2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-10-02). Very rare (popmax 0.00668%, eas); Associated with CIB2-related disorders.

What condition is associated with CIB2 p.Arg33Ter (c.97C>T)?

CIB2 p.Arg33Ter (c.97C>T) is associated with CIB2-related disorders, Usher syndrome (ClinVar).

How common is CIB2 p.Arg33Ter (c.97C>T) in the general population?

CIB2 p.Arg33Ter (c.97C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

CIB2 p.Arg33Ter

c.97C>T · rs201845656 · VCV816953

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00668%, eas)

Conditions

CIB2-related disorders

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 3 of 6
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.33, phastCons 1
Overall
CADD	36.0	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 0.00668% East Asian · 3/44,888 alleles

Filtering AF 0.00426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00428% 69/1,613,778 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,963
European (non-Finnish)	0.00534%	18,728
Remaining individualsnot grpmax-eligible	0.0032%	31,232
South Asian	0.0011%	91,070

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.Arg33Ter
Coding: c.97C>T
MANE Select: NM_006383
dbSNP: rs201845656
Type: single nucleotide variant
Location: chr15:78111266 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 33: 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

CIB2-related disorders

Also linked: Usher syndrome

Similar variants

CIB2 p.Arg33Gln Uncertain significance ★★ ⚠ same residue
CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
CIB2 c.198+1G>A Likely pathogenic ★ same condition
CIB2 c.199-125G>A Likely pathogenic ★ same condition
CIB2 p.Lys4Ter Likely pathogenic ★ same condition
CIB2 p.Arg186Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
CIB2 p.Lys151Asn Conflicting classifications of pathogenicity ★ ⚠ same condition
CIB2 c.199-34C>T Likely benign 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-arg33ter (accessed [today's date]).

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