Is CIT p.Ala1928Val (c.5783C>T) pathogenic?

CIT p.Ala1928Val (c.5783C>T) is classified Uncertain significance in CIT (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6544); Very rare (popmax 0.00445%, eas); Associated with long QT syndrome.

What condition is associated with CIT p.Ala1928Val (c.5783C>T)?

CIT p.Ala1928Val (c.5783C>T) is associated with long QT syndrome (ClinVar).

How common is CIT p.Ala1928Val (c.5783C>T) in the general population?

CIT p.Ala1928Val (c.5783C>T) is very rare (popmax 0.00445%, eas) (gnomAD).

What do computational predictors say about CIT p.Ala1928Val (c.5783C>T)?

AlphaMissense predicts likely pathogenic (score 0.6544) — an in-silico prediction, not a clinical call.

CIT p.Ala1928Val

c.5783C>T · rs776383369 · VCV207961

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00445%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.6544	likely pathogenic
REVEL	0.747	pathogenic-leaning
SaProt	LLR -7.51	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 32 kb · p 1.5e-18 · regional, not allelic
Overall
CADD	29.6	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 A1886V vs ClinVar A1928V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00445% East Asian · 2/44,896 alleles

Filtering AF 0.000738% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000805% 13/1,614,032 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00445%	22,448
Remaining individualsnot grpmax-eligible	0.0032%	31,240
South Asian	0.0022%	45,542
European (non-Finnish)	0.000593%	168,579

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.Ala1928Val
Coding: c.5783C>T
MANE Select: NM_001206999
dbSNP: rs776383369
Type: single nucleotide variant
Location: chr12:119697758 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1928: the 'disordered' region

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

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Ser1929Tyr Uncertain significance ⚠ same condition
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-ala1928val (accessed [today's date]).

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