Is CIT p.Pro1275Ser (c.3823C>T) pathogenic?

CIT p.Pro1275Ser (c.3823C>T) is classified Uncertain significance in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: ambiguous (0.4231); Very rare (popmax 0.00895%, eas); Associated with Inborn genetic diseases.

What condition is associated with CIT p.Pro1275Ser (c.3823C>T)?

CIT p.Pro1275Ser (c.3823C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Pro1275Ser (c.3823C>T) in the general population?

CIT p.Pro1275Ser (c.3823C>T) is very rare (popmax 0.00895%, eas) (gnomAD).

What do computational predictors say about CIT p.Pro1275Ser (c.3823C>T)?

AlphaMissense predicts ambiguous (score 0.4231) — an in-silico prediction, not a clinical call.

CIT p.Pro1275Ser

c.3823C>T · VCV3267447

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4231 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00895%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4231	ambiguous
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 32 kb · p 1.5e-18 · regional, not allelic
Overall
CADD	27.5	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 P1233S vs ClinVar P1275S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00895% East Asian · 4/44,714 alleles

Filtering AF 0.00299% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000344% 5/1,454,406 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00895%	11,179
European (non-Finnish)	8.49e-05%	1,178,028

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.Pro1275Ser
Coding: c.3823C>T
MANE Select: NM_001206999
Type: single nucleotide variant
Location: chr12:119720495 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 1275: the 'interaction with rho/rac' region

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-pro1275ser (accessed [today's date]).

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