Is CIC p.Gln2479Arg (c.7436A>G) pathogenic?

CIC p.Gln2479Arg (c.7436A>G) is classified Uncertain significance in CIC (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-07). AlphaMissense: likely benign (0.089); Very rare (popmax 0.00203%, amr); Associated with Inborn genetic diseases.

What condition is associated with CIC p.Gln2479Arg (c.7436A>G)?

CIC p.Gln2479Arg (c.7436A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CIC p.Gln2479Arg (c.7436A>G) in the general population?

CIC p.Gln2479Arg (c.7436A>G) is very rare (popmax 0.00203%, amr) (gnomAD).

What do computational predictors say about CIC p.Gln2479Arg (c.7436A>G)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

CIC p.Gln2479Arg

c.7436A>G · rs752340916 · VCV2555900

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00203%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.219	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -3, phastCons 0.72
Overall
CADD	17.37	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 is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM Q1570R vs ClinVar Q2479R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00203% Admixed American · 1/49,316 alleles

Filtering AF 0.00019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000125%

Overall 0.000462% 7/1,515,538 alleles · very rare exomes 7/1,368,388 · genomes 0/147,150 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00203%	49,316
European (non-Finnish)	0.000527%	189,662

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.Gln2479Arg
Coding: c.7436A>G
MANE Select: NM_001386298
dbSNP: rs752340916
Type: single nucleotide variant
Location: chr19:42295073 (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

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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-gln2479arg (accessed [today's date]).

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