Is CIB1 p.Ser44fs (c.132del) pathogenic?

CIB1 p.Ser44fs (c.132del) is classified Pathogenic in CIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). Very rare (popmax 0.00017%, nfe).

How common is CIB1 p.Ser44fs (c.132del) in the general population?

CIB1 p.Ser44fs (c.132del) is very rare (popmax 0.00017%, nfe) (gnomAD).

CIB1 p.Ser44fs

c.132del · VCV3692093

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.1	GERP -4.4
Overall
CADD	16.96	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 0.00017% European (non-Finnish) · 2/1,178,844 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,612,314 alleles · very rare exomes 0/1,460,080 · genomes 2/152,234 · joint denominator

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: CIB1
Protein: p.Ser44fs
Coding: c.132del
MANE Select: NM_006384
Type: Deletion
Location: chr15:90232282 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 44: a UniProt-annotated variant site (in)

Full CIB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CIB1 p.Ser44Arg Uncertain significance ★ ⚠ same residue
CIB1 p.Ser44= Likely benign ★ same residue
CIB1 c.465+1del Likely pathogenic ★ same type
CIB1 c.87-29_87-20del Pathogenic ★ same type
CIB1 p.Asp116_Phe117insTer Pathogenic ★ same type
CIB1 p.Asp154fs Likely pathogenic ★ same type
CIB1 p.Gly3fs Pathogenic ★ same type
CIB1 p.Thr79fs Pathogenic ★ 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/cib1-p-ser44fs (accessed [today's date]).

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