Is CIC c.7054+4C>A pathogenic?

CIC c.7054+4C>A is classified Likely benign in CIC (ClinVar, Single submitter, 3 submitters; last evaluated 2023-09-27). Ultra-rare (popmax 0.0495%, mid); Associated with Inborn genetic diseases.

What condition is associated with CIC c.7054+4C>A?

CIC c.7054+4C>A is associated with Inborn genetic diseases, intellectual disability (ClinVar).

How common is CIC c.7054+4C>A in the general population?

CIC c.7054+4C>A is ultra-rare (popmax 0.0495%, mid) (gnomAD).

CIC c.7054+4C>A

rs572168958 · VCV975209

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +4	donor splice region (+4, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.39	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.5	GERP -2.3, phastCons 0.97
Overall
CADD	12.22	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0495% Middle Eastern · 3/6,056 alleles

Filtering AF 0.018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00397% 64/1,612,708 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,019
Admixed American	0.0283%	3,531
African / African-American	0.008%	12,503
Remaining individualsnot grpmax-eligible	0.0064%	15,624
European (non-Finnish)	0.00288%	34,706

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
Coding: c.7054+4C>A
MANE Select: NM_005984 · reported on NM_001386298
dbSNP: rs572168958
Type: single nucleotide variant
Location: chr19:42294308 (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

Also linked: intellectual disability

Similar variants

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
CIC p.Arg1205Trp Uncertain significance ★★ ⚠ same condition
CIC p.Arg1481Gln 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-c-7054-plus-4c-a (accessed [today's date]).

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