Is CIT p.Arg1108= (c.3324A>G) pathogenic?

CIT p.Arg1108= (c.3324A>G) is classified Benign in CIT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-03). Common (popmax 93.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with microcephaly 17, primary, autosomal recessive.

What condition is associated with CIT p.Arg1108= (c.3324A>G)?

CIT p.Arg1108= (c.3324A>G) is associated with microcephaly 17, primary, autosomal recessive (ClinVar).

CIT p.Arg1108=

Q: How common is CIT p.Arg1108= (c.3324A>G) in the general population?

CIT p.Arg1108= (c.3324A>G) is common (popmax 93.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3324A>G · rs278109 · VCV1209742

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 93.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

microcephaly 17, primary, autosomal recessive

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.024	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.78	GERP -0.23, phastCons 1
Overall
CADD	10.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 93.1% African / African-American · 69,584/74,710 alleles

Filtering AF 92.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 92.3%

Overall 81.8% 1,320,099/1,612,962 alleles · common exomes 1,192,187/1,461,650 · genomes 127,912/151,312 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	93.1%	1
Middle Eastern	90%	1
Ashkenazi Jewishnot grpmax-eligible	86.9%	1
Admixed American	84.5%	1
Finnishnot grpmax-eligible	82.4%	1
Remaining individualsnot grpmax-eligible	82.2%	1
European (non-Finnish)	82.1%	1
South Asian	77.2%	1
Amishnot grpmax-eligible	68.3%	1
East Asian	55.8%	2

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
Protein: p.Arg1108=
Coding: c.3324A>G
MANE Select: NM_001206999
dbSNP: rs278109
Type: single nucleotide variant
Location: chr12:119734190 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1108: the 'interaction with rho/rac' region

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

Disease context

microcephaly 17, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Arg220Ter Pathogenic ★★ same condition
CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same condition
CIT p.Ala244Val Uncertain significance ★★ ⚠ same condition
CIT p.Arg1633Cys Uncertain significance ★★ ⚠ same condition
CIT p.Arg23Trp Uncertain significance ★★ ⚠ same condition
CIT p.Arg696Cys Uncertain significance ★★ same condition
CIT p.Asn1301Ser Uncertain significance ★★ ⚠ same condition
CIT p.Asn786Ser 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/cit-p-arg1108 (accessed [today's date]).

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