Is CIB2 p.Ser101fs (c.301_311del) pathogenic?

CIB2 p.Ser101fs (c.301311del) is classified Pathogenic/Likely pathogenic in CIB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-13). Very rare (popmax 0.000772%, nfe); Associated with CIB2-related disorders.

What condition is associated with CIB2 p.Ser101fs (c.301_311del)?

CIB2 p.Ser101fs (c.301_311del) is associated with CIB2-related disorders (ClinVar).

How common is CIB2 p.Ser101fs (c.301_311del) in the general population?

CIB2 p.Ser101fs (c.301_311del) is very rare (popmax 0.000772%, nfe) (gnomAD).

CIB2 p.Ser101fs

c.301_311del · rs1567049981 · VCV1446454

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000772%, nfe)

Conditions

CIB2-related disorders

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 -7.9	GERP -2.8

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000772% European (non-Finnish) · 9/1,165,088 alleles

Filtering AF 0.000363% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000263%

Overall 0.000695% 10/1,438,960 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00165%	60,696
European (non-Finnish)grpmax	0.000772%	129,454

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser101fs
Coding: c.301_311del
MANE Select: NM_006383
dbSNP: rs1567049981
Type: Deletion
Location: chr15:78109270 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 101: the ef-hand 1 domain; a UniProt-annotated variant site (in dfnb48)

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

Disease context

CIB2-related disorders

Similar variants

CIB2 p.Glu100fs Pathogenic/Likely pathogenic ★★ same condition
CIB2 p.Glu105fs Pathogenic/Likely pathogenic ★★ same condition
CIB2 p.Ser101= Benign ★★ same residue
CIB2 p.Ile60fs Likely pathogenic ★ same condition
CIB2 p.Ser101Leu Uncertain significance ★ ⚠ same residue
CIB2 p.Ser101Thr Uncertain significance ★ ⚠ same residue
CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
CIB2 p.Arg33Ter 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-ser101fs (accessed [today's date]).

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