Is CIB2 p.Asn89Ser (c.266A>G) pathogenic?

CIB2 p.Asn89Ser (c.266A>G) is classified Uncertain significance in CIB2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-17). AlphaMissense: likely benign (0.1117); Very rare (popmax 0.00339%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CIB2 p.Asn89Ser (c.266A>G)?

CIB2 p.Asn89Ser (c.266A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CIB2 p.Asn89Ser (c.266A>G) in the general population?

CIB2 p.Asn89Ser (c.266A>G) is very rare (popmax 0.00339%, nfe) (gnomAD).

What do computational predictors say about CIB2 p.Asn89Ser (c.266A>G)?

AlphaMissense predicts likely benign (score 0.1117) — an in-silico prediction, not a clinical call.

CIB2 p.Asn89Ser

c.266A>G · rs768703133 · VCV2579586

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1117 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1117	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.35	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00339% European (non-Finnish) · 40/1,179,728 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00267% 43/1,613,466 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,493
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,470
African / African-American	0.00134%	74,838

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.Asn89Ser
Coding: c.266A>G
MANE Select: NM_006383
dbSNP: rs768703133
Type: single nucleotide variant
Location: chr15:78109315 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 89: the ef-hand 1 domain; 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIB2 p.Asn89= Likely benign ★★ same residue
CIB2 p.Asn89Thr Uncertain significance ★ ⚠ same residue
CIB2 p.Ala76Val Uncertain significance ★★ ⚠ same condition
CIB2 p.Asp18His Uncertain significance ★★ ⚠ same condition
CIB2 p.Asp90Asn Uncertain significance ★★ ⚠ same condition
CIB2 p.Gly162Ser Uncertain significance ★★ ⚠ same condition
CIB2 p.Leu158Trp Uncertain significance ★★ ⚠ same condition
CIB2 p.Met44Val Uncertain significance ★★ ⚠ 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-asn89ser (accessed [today's date]).

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