Is CIT p.Lys647Arg (c.1940A>G) pathogenic?

CIT p.Lys647Arg (c.1940A>G) is classified Uncertain significance in CIT (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-28). AlphaMissense: likely benign (0.162); Ultra-rare (popmax 0.0232%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Lys647Arg (c.1940A>G)?

CIT p.Lys647Arg (c.1940A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Lys647Arg (c.1940A>G) in the general population?

CIT p.Lys647Arg (c.1940A>G) is ultra-rare (popmax 0.0232%, nfe) (gnomAD).

What do computational predictors say about CIT p.Lys647Arg (c.1940A>G)?

AlphaMissense predicts likely benign (score 0.162) — an in-silico prediction, not a clinical call.

CIT p.Lys647Arg

c.1940A>G · rs144005700 · VCV2569928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.162 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0232%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.162	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.44 · evaluated, not missing
Pangolin	Δ0.29	gain · loss 0.11 · SpliceAI below 0.2 · independent
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 55 kb · p 2.1e-24 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0232% European (non-Finnish) · 274/1,179,128 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0201%

Overall 0.0177% 285/1,613,042 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0232%	4,303
Remaining individualsnot grpmax-eligible	0.0112%	8,923
African / African-American	0.00534%	18,724

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.Lys647Arg
Coding: c.1940A>G
MANE Select: NM_001206999
dbSNP: rs144005700
Type: single nucleotide variant
Location: chr12:119775787 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
CIT p.Arg1861Cys 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-lys647arg (accessed [today's date]).

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