Is CIT p.Arg1233Lys (c.3698G>A) pathogenic?

CIT p.Arg1233Lys (c.3698G>A) is classified Uncertain significance in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-27). AlphaMissense: ambiguous (0.4051); Absent from gnomAD v4.1.

How common is CIT p.Arg1233Lys (c.3698G>A) in the general population?

CIT p.Arg1233Lys (c.3698G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIT p.Arg1233Lys (c.3698G>A)?

AlphaMissense predicts ambiguous (score 0.4051) — an in-silico prediction, not a clinical call.

CIT p.Arg1233Lys

c.3698G>A · rs1957806995 · VCV1810058

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4051 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4051	ambiguous
REVEL	0.114	moderately benign-leaning
SaProt	LLR -3.65	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.32	constrained · MANE · 841 bp · p 5.7e-06 · regional, not allelic
Overall
CADD	24.6	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 R1191K vs ClinVar R1233K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CIT
Protein: p.Arg1233Lys
Coding: c.3698G>A
MANE Select: NM_001206999
dbSNP: rs1957806995
Type: single nucleotide variant
Location: chr12:119721343 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1233: the 'interaction with rho/rac' region

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

Similar variants

CIT p.Arg1178Ter Pathogenic ★★ same type
CIT p.Arg220Ter Pathogenic ★★ same type
CIT c.4168+5G>A Uncertain significance ★★ same type
CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same type
CIT p.Ala1466Asp Uncertain significance ★★ ⚠ same type
CIT p.Ala1527Val Uncertain significance ★★ ⚠ same type
CIT p.Ala244Val Uncertain significance ★★ ⚠ same type
CIT p.Ala495Ser 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-p-arg1233lys (accessed [today's date]).

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