Is CIC p.Ala2339Gly (c.7016C>G) pathogenic?

CIC p.Ala2339Gly (c.7016C>G) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-27). AlphaMissense: likely pathogenic (0.9149); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 45.

What condition is associated with CIC p.Ala2339Gly (c.7016C>G)?

CIC p.Ala2339Gly (c.7016C>G) is associated with intellectual developmental disorder, autosomal dominant 45 (ClinVar).

How common is CIC p.Ala2339Gly (c.7016C>G) in the general population?

CIC p.Ala2339Gly (c.7016C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIC p.Ala2339Gly (c.7016C>G)?

AlphaMissense predicts likely pathogenic (score 0.9149) — an in-silico prediction, not a clinical call.

CIC p.Ala2339Gly

c.7016C>G · VCV4078293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9149 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

intellectual developmental disorder, autosomal dominant 45

Computational evidence

Protein change
AlphaMissense	0.9149	likely pathogenic
REVEL	0.239	benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.24	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.7	GERP 1.4, phastCons 1
Overall
CADD	26.3	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 A1430G vs ClinVar A2339G) — 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.Ala2339Gly
Coding: c.7016C>G
MANE Select: NM_005984 · reported on NM_001386298
Type: single nucleotide variant
Location: chr19:42294266 (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-ala2339gly (accessed [today's date]).

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