Is CIT p.Ala1836Thr (c.5506G>A) pathogenic?

CIT p.Ala1836Thr (c.5506G>A) is classified Likely benign in CIT (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0594); Rare (popmax 0.566%, afr); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Ala1836Thr (c.5506G>A)?

CIT p.Ala1836Thr (c.5506G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Ala1836Thr (c.5506G>A) in the general population?

CIT p.Ala1836Thr (c.5506G>A) is rare (popmax 0.566%, afr) (gnomAD).

What do computational predictors say about CIT p.Ala1836Thr (c.5506G>A)?

AlphaMissense predicts likely benign (score 0.0594) — an in-silico prediction, not a clinical call.

CIT p.Ala1836Thr

c.5506G>A · rs149158991 · VCV791323

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.0594 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.566%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0594	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.01	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 -0.63	GERP -2.6
Regional constraint	o/e 0.73	unconstrained · MANE · 32 kb · p 1.5e-18 · regional, not allelic
Overall
CADD	10.63	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 A1794T vs ClinVar A1836T) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.566% African / African-American · 425/75,050 alleles

Filtering AF 0.522% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.504%

Overall 0.0549% 886/1,614,188 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.566%	177
Remaining individualsnot grpmax-eligible	0.072%	1,389
Admixed American	0.06%	1,667
Middle Eastern	0.0495%	2,021
Finnishnot grpmax-eligible	0.0406%	2,463
European (non-Finnish)	0.0295%	3,391
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,874
South Asian	0.0011%	91,086

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.Ala1836Thr
Coding: c.5506G>A
MANE Select: NM_001206999
dbSNP: rs149158991
Type: single nucleotide variant
Location: chr12:119701660 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1836: the cnh 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.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-ala1836thr (accessed [today's date]).

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