Is CIB2 p.Lys151Asn (c.453G>C) pathogenic?

CIB2 p.Lys151Asn (c.453G>C) is classified Conflicting classifications of pathogenicity in CIB2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-03-27). AlphaMissense: likely pathogenic (0.9694); Ultra-rare (popmax 0.066%, mid); Associated with CIB2-related disorders.

What condition is associated with CIB2 p.Lys151Asn (c.453G>C)?

CIB2 p.Lys151Asn (c.453G>C) is associated with CIB2-related disorders (ClinVar).

How common is CIB2 p.Lys151Asn (c.453G>C) in the general population?

CIB2 p.Lys151Asn (c.453G>C) is ultra-rare (popmax 0.066%, mid) (gnomAD).

What do computational predictors say about CIB2 p.Lys151Asn (c.453G>C)?

AlphaMissense predicts likely pathogenic (score 0.9694) — an in-silico prediction, not a clinical call.

CIB2 p.Lys151Asn

c.453G>C · rs747085927 · VCV1487394

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9694 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CIB2-related disorders

Computational evidence

Protein change
AlphaMissense	0.9694	likely pathogenic
REVEL	0.421	indeterminate
SaProt	LLR -9.84	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.7	GERP -1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,060 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.00217% 35/1,614,200 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,515
South Asian	0.0285%	3,503
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000339%	295,005

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.Lys151Asn
Coding: c.453G>C
MANE Select: NM_006383
dbSNP: rs747085927
Type: single nucleotide variant
Location: chr15:78105828 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 151: a UniProt-annotated variant site (in dfnb48); a UniProt-annotated variant site (in dfnb48; uncertain significance); the ef-hand 3 domain; an α-helix

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

Disease context

CIB2-related disorders

Similar variants

CIB2 p.Lys151Glu Uncertain significance ★ ⚠ same residue
CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same condition
CIB2 p.Arg33Ter 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 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-lys151asn (accessed [today's date]).

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