Is CIC p.Asp595Glu (c.1785C>A) pathogenic?

CIC p.Asp595Glu (c.1785C>A) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-26). Absent from gnomAD v4.1; Associated with intellectual developmental disorder, autosomal dominant 45.

What condition is associated with CIC p.Asp595Glu (c.1785C>A)?

CIC p.Asp595Glu (c.1785C>A) is associated with intellectual developmental disorder, autosomal dominant 45 (ClinVar).

How common is CIC p.Asp595Glu (c.1785C>A) in the general population?

CIC p.Asp595Glu (c.1785C>A) is absent from gnomAD v4.1 (gnomAD).

CIC p.Asp595Glu

c.1785C>A · rs975540618 · VCV1342450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 398,570)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -2.5
Overall
CADD	4.677	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 398,570). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CIC
Protein: p.Asp595Glu
Coding: c.1785C>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs975540618
Type: single nucleotide variant
Location: chr19:42273568 (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-asp595glu (accessed [today's date]).

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