What condition is associated with CIT p.Pro158Arg (c.473C>G)?

CIT p.Pro158Arg (c.473C>G) is associated with autosomal recessive primary microcephaly (ClinVar).

How common is CIT p.Pro158Arg (c.473C>G) in the general population?

CIT p.Pro158Arg (c.473C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIT p.Pro158Arg (c.473C>G)?

AlphaMissense predicts likely pathogenic (score 0.9512) — an in-silico prediction, not a clinical call.

CIT p.Pro158Arg

Q: Is CIT p.Pro158Arg (c.473C>G) pathogenic?

CIT p.Pro158Arg (c.473C>G) is classified Pathogenic in CIT (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9512); Absent from gnomAD v4.1; Associated with autosomal recessive primary microcephaly.

c.473C>G · rs879255524 · VCV252994

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9512 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

autosomal recessive primary microcephaly

Computational evidence

Protein change
AlphaMissense	0.9512	likely pathogenic ✓ concordant with ClinVar
REVEL	0.43	indeterminate
SaProt	LLR -11.55	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.5, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	28.3	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.Pro158Arg
Coding: c.473C>G
MANE Select: NM_001206999
dbSNP: rs879255524
Type: single nucleotide variant
Location: chr12:119850217 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 158: the protein kinase domain

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

Disease context

autosomal recessive primary microcephaly — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT c.1111+1G>A Pathogenic ★ same condition
CIT p.Gln138Ter Pathogenic same condition
CIT p.Asn10fs Likely pathogenic ★ 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

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-pro158arg (accessed [today's date]).

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