Is CIC p.Arg2080Gln (c.6239G>A) pathogenic?

CIC p.Arg2080Gln (c.6239G>A) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-12). AlphaMissense: likely benign (0.2112); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with CIC p.Arg2080Gln (c.6239G>A)?

CIC p.Arg2080Gln (c.6239G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CIC p.Arg2080Gln (c.6239G>A) in the general population?

CIC p.Arg2080Gln (c.6239G>A) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CIC p.Arg2080Gln (c.6239G>A)?

AlphaMissense predicts likely benign (score 0.2112) — an in-silico prediction, not a clinical call.

CIC p.Arg2080Gln

c.6239G>A · rs2038253762 · VCV3144970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2112 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2112	likely benign
REVEL	0.111	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	26.1	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 R1171Q vs ClinVar R2080Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,994 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000496% 8/1,613,442 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,998
African / African-American	0.00267%	37,471
Remaining individualsnot grpmax-eligible	0.0016%	62,468
European (non-Finnish)	0.000169%	590,002

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.Arg2080Gln
Coding: c.6239G>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs2038253762
Type: single nucleotide variant
Location: chr19:42292998 (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.Arg2080Trp Uncertain significance ★ ⚠ same residue
CIC p.Arg2080= Benign/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

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-arg2080gln (accessed [today's date]).

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