Is CIT c.753+8del pathogenic?

CIT c.753+8del is classified Conflicting classifications of pathogenicity in CIT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-07-01). Rare (popmax 0.169%, nfe); Associated with intellectual disability.

What condition is associated with CIT c.753+8del?

CIT c.753+8del is associated with intellectual disability (ClinVar).

How common is CIT c.753+8del in the general population?

CIT c.753+8del is rare (popmax 0.169%, nfe) (gnomAD).

CIT c.753+8del

rs771292782 · VCV493126

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.169%, nfe)

Conditions

intellectual disability

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +8	near-intronic (+8 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.27	GERP 0.72
Non-coding constraint	Z 2.44	1 kb window · o/e 0.82 · regional · uncalibrated
Overall
CADD	4.371	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.169% European (non-Finnish) · 1,986/1,174,240 alleles

Filtering AF 0.163% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.16%

Overall 0.144% 2,323/1,607,672 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.18%	556
European (non-Finnish)grpmax	0.169%	591
South Asian	0.13%	771
Remaining individualsnot grpmax-eligible	0.111%	902
African / African-American	0.0334%	2,995
Admixed American	0.015%	6,666
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,566

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CIT
Coding: c.753+8del
MANE Select: NM_001206999
dbSNP: rs771292782
Type: Deletion
Location: chr12:119832763 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Asn1164Ser Conflicting classifications of pathogenicity ★ ⚠ same condition
CIT c.239-9del Likely benign ★★ same type
CIT c.2532-6del Benign/Likely benign ★★ same type
CIT p.Asn10fs Likely pathogenic ★ same type
CIT p.Asp1541fs Pathogenic ★ same type
CIT p.Glu204_Leu205insTer Pathogenic ★ same type
CIT p.Val397fs Pathogenic ★ same type
CIT p.Glu225_Val229del Uncertain significance ★ 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/cit-c-753-plus-8del (accessed [today's date]).

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