Is CIT p.Arg9Gln (c.26G>A) pathogenic?

CIT p.Arg9Gln (c.26G>A) is classified Benign/Likely benign in CIT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-12). AlphaMissense: likely benign (0.1083); Rare (popmax 0.681%, nfe).

How common is CIT p.Arg9Gln (c.26G>A) in the general population?

CIT p.Arg9Gln (c.26G>A) is rare (popmax 0.681%, nfe) (gnomAD).

What do computational predictors say about CIT p.Arg9Gln (c.26G>A)?

AlphaMissense predicts likely benign (score 0.1083) — an in-silico prediction, not a clinical call.

CIT p.Arg9Gln

c.26G>A · rs56193743 · VCV715456

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.1083 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.681%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1083	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -6.21	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 4.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	23.0	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 0.681% European (non-Finnish) · 8,037/1,179,744 alleles

Filtering AF 0.669% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.664%

Overall 0.582% 9,386/1,613,638 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	4.95%	20
European (non-Finnish)grpmax	0.681%	147
South Asian	0.547%	183
Remaining individualsnot grpmax-eligible	0.48%	208
Finnishnot grpmax-eligible	0.284%	352
Middle Eastern	0.28%	357
Admixed American	0.233%	428
Ashkenazi Jewishnot grpmax-eligible	0.233%	429
African / African-American	0.124%	807
East Asian	0.0112%	8,968

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg9Gln
Coding: c.26G>A
MANE Select: NM_001206999
dbSNP: rs56193743
Type: single nucleotide variant
Location: chr12:119876143 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 9: a UniProt-annotated variant site (in)

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

Similar variants

CIT p.Arg9Trp Uncertain significance ★ ⚠ same residue
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

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-arg9gln (accessed [today's date]).

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