Is CIC p.Arg1481Gln (c.4442G>A) pathogenic?

CIC p.Arg1481Gln (c.4442G>A) is classified Uncertain significance in CIC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-03-13). AlphaMissense: likely benign (0.0912); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CIC p.Arg1481Gln (c.4442G>A)?

CIC p.Arg1481Gln (c.4442G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CIC p.Arg1481Gln (c.4442G>A) in the general population?

CIC p.Arg1481Gln (c.4442G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CIC p.Arg1481Gln (c.4442G>A)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

CIC p.Arg1481Gln

c.4442G>A · VCV4002948

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.118	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 1.5, phastCons 1
Overall
CADD	22.0	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 R572Q vs ClinVar R1481Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.0013% 21/1,613,616 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,880
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,454
Finnishnot grpmax-eligible	0.00156%	63,968
European (non-Finnish)	0.00144%	69,409

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.Arg1481Gln
Coding: c.4442G>A
MANE Select: NM_005984 · reported on NM_001386298
Type: single nucleotide variant
Location: chr19:42290483 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIC p.Arg1481= Likely benign ★ same residue
CIC c.2795-2056C>T Uncertain significance ★★ same condition
CIC p.Ala1228Val Uncertain significance ★★ ⚠ same condition
CIC p.Ala1445Gly Uncertain significance ★★ ⚠ same condition
CIC p.Ala1750Val Uncertain significance ★★ ⚠ same condition
CIC p.Ala1975Gly Uncertain significance ★★ ⚠ same condition
CIC p.Ala2463Thr Uncertain significance ★★ ⚠ same condition
CIC p.Arg1205Trp 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-arg1481gln (accessed [today's date]).

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