Is CIB1 p.Asp154fs (c.461del) pathogenic?

CIB1 p.Asp154fs (c.461del) is classified Likely pathogenic in CIB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-22). Associated with Susceptibility to severe COVID-19.

What condition is associated with CIB1 p.Asp154fs (c.461del)?

CIB1 p.Asp154fs (c.461del) is associated with Susceptibility to severe COVID-19 (ClinVar).

CIB1 p.Asp154fs

c.461del · VCV3256944

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Susceptibility to severe COVID-19

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 5 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.6	GERP 0.3, phastCons 1

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

Variant & gene context

Gene: CIB1
Protein: p.Asp154fs
Coding: c.461del
MANE Select: NM_006384
Type: Deletion
Location: chr15:90231099 (GRCh38)
Gene constraint: LOEUF 1.233 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.37 · 9 PDB
Residue 154: a UniProt-annotated variant site (in ev3; absence of cib1 protein in homozygous patient cells); the ef-hand 2 domain; an α-helix

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

Disease context

Susceptibility to severe COVID-19

Similar variants

CIB1 p.Asp154His Uncertain significance ★★ ⚠ same residue
CIB1 c.465+1del Likely pathogenic ★ same condition
CIB1 p.Asp154Tyr Uncertain significance ★ ⚠ same residue
GDPGP1 p.Leu154Met Uncertain significance ★ ⚠ same residue
CIB1 c.87-37T>G Uncertain significance ★ same condition
CIB1 c.87-36C>T Likely benign same condition
CIB1 c.87-29_87-20del Pathogenic ★ same type
CIB1 p.Asp116_Phe117insTer 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-asp154fs (accessed [today's date]).

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