Is CIC p.Gly1018Arg (c.3052G>A) pathogenic?

CIC p.Gly1018Arg (c.3052G>A) is classified Likely benign in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-01). AlphaMissense: likely benign (0.3312); Ultra-rare (popmax 0.0213%, afr).

How common is CIC p.Gly1018Arg (c.3052G>A) in the general population?

CIC p.Gly1018Arg (c.3052G>A) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about CIC p.Gly1018Arg (c.3052G>A)?

AlphaMissense predicts likely benign (score 0.3312) — an in-silico prediction, not a clinical call.

CIC p.Gly1018Arg

c.3052G>A · VCV3770864

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3312 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.3312	likely benign
REVEL	0.266	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 11	GERP 1.2, phastCons 1
Overall
CADD	26.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM G109R vs ClinVar G1018R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0213% African / African-American · 16/75,022 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00254% 41/1,613,524 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,689
Middle Eastern	0.017%	5,898
Admixed American	0.005%	20,010
Remaining individualsnot grpmax-eligible	0.0032%	31,238
South Asian	0.0022%	45,535
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.Gly1018Arg
Coding: c.3052G>A
MANE Select: NM_005984 · reported on NM_001386298
Type: single nucleotide variant
Location: chr19:42287113 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Similar variants

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CIC p.Asn1136Ser Likely pathogenic ★★ same type
CIC p.Gln1134Ter Pathogenic ★★ same type
CIC p.Gln1799Ter Likely pathogenic ★★ same type
SLC25A1 c.821+1G>A Pathogenic ★★ same type
SLC25A1 p.Ala274Val Pathogenic/Likely pathogenic ★★ same type

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-gly1018arg (accessed [today's date]).

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