Is CIC p.Ala2398Val (c.7193C>T) pathogenic?

CIC p.Ala2398Val (c.7193C>T) is classified Uncertain significance in CIC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). AlphaMissense: likely pathogenic (0.9581); Very rare (popmax 0.000169%, nfe).

How common is CIC p.Ala2398Val (c.7193C>T) in the general population?

CIC p.Ala2398Val (c.7193C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about CIC p.Ala2398Val (c.7193C>T)?

AlphaMissense predicts likely pathogenic (score 0.9581) — an in-silico prediction, not a clinical call.

CIC p.Ala2398Val

c.7193C>T · rs774512722 · VCV1694926

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9581 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
AlphaMissense	0.9581	likely pathogenic
REVEL	0.382	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.5, phastCons 1
Overall
CADD	26.3	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 A1489V vs ClinVar A2398V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,179,958 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,450,304 alleles · very rare

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.Ala2398Val
Coding: c.7193C>T
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs774512722
Type: single nucleotide variant
Location: chr19:42294830 (GRCh38)
Structure: AlphaFold pLDDT 75.09

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

Similar variants

CIC c.3179+1G>A Likely pathogenic ★★ same type
CIC c.3179+1G>T Pathogenic ★★ same type
CIC c.5903-2A>G Likely pathogenic ★★ same type
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-ala2398val (accessed [today's date]).

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