Is CIB2 p.Lys24Asn (c.72G>C) pathogenic?

CIB2 p.Lys24Asn (c.72G>C) is classified Uncertain significance in CIB2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-03). AlphaMissense: likely pathogenic (0.992); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CIB2 p.Lys24Asn (c.72G>C)?

CIB2 p.Lys24Asn (c.72G>C) is associated with Inborn genetic diseases (ClinVar).

How common is CIB2 p.Lys24Asn (c.72G>C) in the general population?

CIB2 p.Lys24Asn (c.72G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIB2 p.Lys24Asn (c.72G>C)?

AlphaMissense predicts likely pathogenic (score 0.992) — an in-silico prediction, not a clinical call.

CIB2 p.Lys24Asn

c.72G>C · rs2074348685 · VCV2277946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.992 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.992	likely pathogenic
REVEL	0.119	moderately benign-leaning
SaProt	LLR -10.46	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 26 kb · p 0.17 · regional, not allelic
Overall
CADD	26.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CIB2
Protein: p.Lys24Asn
Coding: c.72G>C
MANE Select: NM_006383
dbSNP: rs2074348685
Type: single nucleotide variant
Location: chr15:78123719 (GRCh38)
Gene constraint: LOEUF 1.274 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.71 · 1 PDB
Residue 24: 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.Lys24Thr Uncertain significance ★ ⚠ same residue
CIB2 p.Ala76Val Uncertain significance ★★ ⚠ same condition
CIB2 p.Asn89Ser 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-lys24asn (accessed [today's date]).

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