Is CIC p.Lys2249= (c.6747G>A) pathogenic?

CIC p.Lys2249= (c.6747G>A) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-20). Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 45.

What condition is associated with CIC p.Lys2249= (c.6747G>A)?

CIC p.Lys2249= (c.6747G>A) is associated with intellectual developmental disorder, autosomal dominant 45 (ClinVar).

How common is CIC p.Lys2249= (c.6747G>A) in the general population?

CIC p.Lys2249= (c.6747G>A) is absent from gnomAD v4.1 (gnomAD).

CIC p.Lys2249=

c.6747G>A · rs2038327689 · VCV1030470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

intellectual developmental disorder, autosomal dominant 45

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.9	GERP 1.5, phastCons 1
Overall
CADD	15.44	PHRED · no single calibrated threshold — expert panels disagree

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: CIC
Protein: p.Lys2249=
Coding: c.6747G>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs2038327689
Type: single nucleotide variant
Location: chr19:42293816 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

intellectual developmental disorder, autosomal dominant 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIC c.3179+1G>T Pathogenic ★★ same condition
CIC c.5903-2A>G Likely pathogenic ★★ same condition
CIC p.Asn1136Ser Likely pathogenic ★★ same condition
CIC p.Gln1134Ter Pathogenic ★★ same condition
CIC p.Gln1799Ter Likely pathogenic ★★ same condition
CIC p.Ala1761Val Uncertain significance ★★ ⚠ same condition
CIC p.Ala2064Thr Uncertain significance ★★ ⚠ same condition
CIC p.Ala2463Thr 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/cic-p-lys2249 (accessed [today's date]).

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