Is CIC p.Ile1064Val (c.3190A>G) pathogenic?

CIC p.Ile1064Val (c.3190A>G) is classified Likely benign in CIC (ClinVar, No assertion criteria, 2 submitters; last evaluated 2023-06-20). AlphaMissense: likely benign (0.1657); Ultra-rare (popmax 0.0423%, eas); Associated with CIC-related disorder.

What condition is associated with CIC p.Ile1064Val (c.3190A>G)?

CIC p.Ile1064Val (c.3190A>G) is associated with CIC-related disorder (ClinVar).

How common is CIC p.Ile1064Val (c.3190A>G) in the general population?

CIC p.Ile1064Val (c.3190A>G) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

What do computational predictors say about CIC p.Ile1064Val (c.3190A>G)?

AlphaMissense predicts likely benign (score 0.1657) — an in-silico prediction, not a clinical call.

CIC p.Ile1064Val

c.3190A>G · rs199958449 · VCV133919

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

CIC-related disorder

Computational evidence

Protein change
AlphaMissense	0.1657	likely benign
REVEL	0.105	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7	GERP 0.27, phastCons 1
Overall
CADD	19.79	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 I155V vs ClinVar I1064V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0423% East Asian · 19/44,870 alleles

Filtering AF 0.0277% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00198% 32/1,614,062 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,362
Remaining individualsnot grpmax-eligible	0.0192%	5,208
European (non-Finnish)	8.47e-05%	1,180,018

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.Ile1064Val
Coding: c.3190A>G
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs199958449
Type: single nucleotide variant
Location: chr19:42287330 (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.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.Arg800His Uncertain significance ★★ same condition
CIC p.Gly17Val Uncertain significance ★★ same condition
CIC p.Val989Ala Uncertain significance ★★ same condition
CIC p.Arg800Cys Likely pathogenic ★ 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-ile1064val (accessed [today's date]).

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