Is CIB2 p.Asn109Lys (c.327C>G) pathogenic?

CIB2 p.Asn109Lys (c.327C>G) is classified Uncertain significance in CIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-06). AlphaMissense: ambiguous (0.4777); Very rare (popmax 0.0011%, sas).

How common is CIB2 p.Asn109Lys (c.327C>G) in the general population?

CIB2 p.Asn109Lys (c.327C>G) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CIB2 p.Asn109Lys (c.327C>G)?

AlphaMissense predicts ambiguous (score 0.4777) — an in-silico prediction, not a clinical call.

CIB2 p.Asn109Lys

c.327C>G · rs2141887089 · VCV1475871

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4777 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4777	ambiguous
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.30	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.85	donor gain · deltas
Pangolin	Δ0.35	gain · loss 0.13 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 3.1	GERP 0.35, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	25.1	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 0.0011% South Asian · 1/90,896 alleles

Overall 6.85e-05% 1/1,460,876 alleles · very rare

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.Asn109Lys
Coding: c.327C>G
MANE Select: NM_006383
dbSNP: rs2141887089
Type: single nucleotide variant
Location: chr15:78109254 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 109: a UniProt-annotated variant site (in dfnb48); the ef-hand 2 domain; an α-helix

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

Similar variants

CIB2 p.Asn109Ser Uncertain significance ★ same residue
CIB2 p.Arg104Ter Pathogenic/Likely pathogenic ★★ same type
CIB2 p.Arg33Ter Pathogenic ★★ same type
CIB2 p.Arg66Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
CIB2 c.198+3A>G Uncertain significance ★★ same type
CIB2 p.Ala108Thr Uncertain significance ★★ ⚠ same type
CIB2 p.Ala76Val Uncertain significance ★★ ⚠ same type
CIB2 p.Arg134Gln Uncertain significance ★★ ⚠ 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/cib2-p-asn109lys (accessed [today's date]).

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