Is CIT p.Ser395Trp (c.1184C>G) pathogenic?

CIT p.Ser395Trp (c.1184C>G) is classified Uncertain significance in CIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.1733); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CIT p.Ser395Trp (c.1184C>G)?

CIT p.Ser395Trp (c.1184C>G) is associated with Inborn genetic diseases (ClinVar).

How common is CIT p.Ser395Trp (c.1184C>G) in the general population?

CIT p.Ser395Trp (c.1184C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIT p.Ser395Trp (c.1184C>G)?

AlphaMissense predicts likely benign (score 0.1733) — an in-silico prediction, not a clinical call.

CIT p.Ser395Trp

c.1184C>G · rs752750796 · VCV2294777

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1733 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1733	likely benign
REVEL	0.23	benign-leaning
SaProt	LLR -10.46	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	29.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CIT
Protein: p.Ser395Trp
Coding: c.1184C>G
MANE Select: NM_001206999
dbSNP: rs752750796
Type: single nucleotide variant
Location: chr12:119803317 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 395: the agc-kinase c-terminal 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.Ser395= Likely benign ★ same residue
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

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-ser395trp (accessed [today's date]).

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