Is CIT p.Arg151Gln (c.452G>A) pathogenic?

CIT p.Arg151Gln (c.452G>A) is classified Benign/Likely benign in CIT (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-10). AlphaMissense: likely benign (0.0681); Low-frequency (popmax 2.08%, afr).

How common is CIT p.Arg151Gln (c.452G>A) in the general population?

CIT p.Arg151Gln (c.452G>A) is low-frequency (popmax 2.08%, afr) (gnomAD).

What do computational predictors say about CIT p.Arg151Gln (c.452G>A)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

CIT p.Arg151Gln

c.452G>A · rs61735296 · VCV784260

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.08%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -5.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -2.9
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	7.05	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 2.08% African / African-American · 1,556/74,798 alleles

Filtering AF 1.99% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.96%

Overall 0.109% 1,765/1,613,138 alleles · low-frequency exomes 852/1,461,444 · genomes 913/151,694 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.08%	48
Remaining individualsnot grpmax-eligible	0.168%	595
Middle Eastern	0.116%	865
Admixed American	0.112%	895
South Asian	0.00659%	15,175
East Asian	0.00223%	44,852
European (non-Finnish)	0.00195%	51,287

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.Arg151Gln
Coding: c.452G>A
MANE Select: NM_001206999
dbSNP: rs61735296
Type: single nucleotide variant
Location: chr12:119850238 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 151: the protein kinase domain

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-arg151gln (accessed [today's date]).

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