Is CIC p.Arg800His (c.2399G>A) pathogenic?

CIC p.Arg800His (c.2399G>A) is classified Uncertain significance in CIC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-05-12). Very rare (popmax 0.00221%, nfe); Associated with CIC-related disorder.

What condition is associated with CIC p.Arg800His (c.2399G>A)?

CIC p.Arg800His (c.2399G>A) is associated with CIC-related disorder (ClinVar).

How common is CIC p.Arg800His (c.2399G>A) in the general population?

CIC p.Arg800His (c.2399G>A) is very rare (popmax 0.00221%, nfe) (gnomAD).

CIC p.Arg800His

c.2399G>A · rs1193038690 · VCV2628980

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00221%, nfe)

Conditions

CIC-related disorder

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 12	GERP 1.5, phastCons 1
Overall
CADD	29.3	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00221% European (non-Finnish) · 5/226,398 alleles

Filtering AF 0.000846% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00047%

Overall 0.00175% 7/399,012 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00541%	18,472
European (non-Finnish)grpmax	0.00221%	45,280
African / African-American	0.00206%	48,656

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CIC
Protein: p.Arg800His
Coding: c.2399G>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs1193038690
Type: single nucleotide variant
Location: chr19:42274182 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

CIC-related disorder

Similar variants

CIC p.Arg800Cys Likely pathogenic ★ same residue
CIC p.Asn1136Ser Likely pathogenic ★★ same condition
SLC25A1 p.Ala274Val Pathogenic/Likely pathogenic ★★ same condition
SLC25A1 p.Glu174Ter Pathogenic/Likely pathogenic ★★ same condition
CIC p.Arg2114Trp Uncertain significance ★★ ⚠ same condition
CIC p.Gly17Val Uncertain significance ★★ same condition
CIC p.Val989Ala Uncertain significance ★★ ⚠ same condition
CIC c.7186+3G>T 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-arg800his (accessed [today's date]).

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