Is CIC p.Glu1276Gln (c.3826G>C) pathogenic?

CIC p.Glu1276Gln (c.3826G>C) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely benign (0.1833); Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 45.

What condition is associated with CIC p.Glu1276Gln (c.3826G>C)?

CIC p.Glu1276Gln (c.3826G>C) is associated with intellectual developmental disorder, autosomal dominant 45 (ClinVar).

How common is CIC p.Glu1276Gln (c.3826G>C) in the general population?

CIC p.Glu1276Gln (c.3826G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIC p.Glu1276Gln (c.3826G>C)?

AlphaMissense predicts likely benign (score 0.1833) — an in-silico prediction, not a clinical call.

CIC p.Glu1276Gln

c.3826G>C · VCV3341300

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1833 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

intellectual developmental disorder, autosomal dominant 45

Computational evidence

Protein change
AlphaMissense	0.1833	likely benign
REVEL	0.16	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E367Q vs ClinVar E1276Q) — 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.Glu1276Gln
Coding: c.3826G>C
MANE Select: NM_005984 · reported on NM_001386298
Type: single nucleotide variant
Location: chr19:42289055 (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-glu1276gln (accessed [today's date]).

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