Is CIC p.Lys2340Gln (c.7018A>C) pathogenic?

CIC p.Lys2340Gln (c.7018A>C) is classified Likely benign in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-17). AlphaMissense: likely pathogenic (0.9139); Absent from gnomAD v4.1; Associated with autism spectrum disorder.

What condition is associated with CIC p.Lys2340Gln (c.7018A>C)?

CIC p.Lys2340Gln (c.7018A>C) is associated with autism spectrum disorder (ClinVar).

How common is CIC p.Lys2340Gln (c.7018A>C) in the general population?

CIC p.Lys2340Gln (c.7018A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIC p.Lys2340Gln (c.7018A>C)?

AlphaMissense predicts likely pathogenic (score 0.9139) — an in-silico prediction, not a clinical call.

CIC p.Lys2340Gln

c.7018A>C · rs2514083473 · VCV2429814

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9139 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

autism spectrum disorder

Computational evidence

Protein change
AlphaMissense	0.9139	likely pathogenic
REVEL	0.182	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K1431Q vs ClinVar K2340Q) — verify the residue.

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.Lys2340Gln
Coding: c.7018A>C
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs2514083473
Type: single nucleotide variant
Location: chr19:42294268 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIC p.Arg659Cys Likely benign ★ same condition
CIC p.Thr1661fs Likely pathogenic ★ same condition
CIC p.Pro711_Glu717delinsThrMet Likely benign ★ same condition
CIC c.3179+1G>A Likely pathogenic ★★ same type
CIC c.3179+1G>T Pathogenic ★★ same type
CIC c.5903-2A>G Likely pathogenic ★★ same type
CIC p.Asn1136Ser Likely pathogenic ★★ same type
CIC p.Gln1134Ter Pathogenic ★★ 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/cic-p-lys2340gln (accessed [today's date]).

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