Is CIT p.Arg231Leu (c.692G>T) pathogenic?

CIT p.Arg231Leu (c.692G>T) is classified Uncertain significance in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-17). AlphaMissense: likely pathogenic (0.7209); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Arg231Leu (c.692G>T)?

CIT p.Arg231Leu (c.692G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Arg231Leu (c.692G>T) in the general population?

CIT p.Arg231Leu (c.692G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about CIT p.Arg231Leu (c.692G>T)?

AlphaMissense predicts likely pathogenic (score 0.7209) — an in-silico prediction, not a clinical call.

CIT p.Arg231Leu

c.692G>T · VCV3267449

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7209 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7209	likely pathogenic
REVEL	0.573	indeterminate
SaProt	LLR -8.70	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,064 alleles

Overall 6.84e-05% 1/1,461,614 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: CIT
Protein: p.Arg231Leu
Coding: c.692G>T
MANE Select: NM_001206999
Type: single nucleotide variant
Location: chr12:119832832 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 231: the protein kinase domain

Full CIT 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

Similar variants

CIT p.Arg231His Uncertain significance ★★ ⚠ same residue
CIT p.Arg1178Ter Pathogenic ★★ same condition
CIT c.4168+5G>A Uncertain significance ★★ same condition
CIT p.Ala1527Val Uncertain significance ★★ ⚠ same condition
CIT p.Ala495Ser Uncertain significance ★★ ⚠ same condition
CIT p.Ala8Val Uncertain significance ★★ ⚠ same condition
CIT p.Arg100Gly Uncertain significance ★★ ⚠ same condition
CIT p.Arg1469Cys 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-arg231leu (accessed [today's date]).

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