Is CIT p.Asp230Val (c.689A>T) pathogenic?

CIT p.Asp230Val (c.689A>T) is classified Pathogenic in CIT (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-09-02). AlphaMissense: likely pathogenic (0.9887); Absent from gnomAD v4.1; Associated with microcephaly 17, primary, autosomal recessive.

What condition is associated with CIT p.Asp230Val (c.689A>T)?

CIT p.Asp230Val (c.689A>T) is associated with microcephaly 17, primary, autosomal recessive (ClinVar).

How common is CIT p.Asp230Val (c.689A>T) in the general population?

CIT p.Asp230Val (c.689A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CIT p.Asp230Val (c.689A>T)?

AlphaMissense predicts likely pathogenic (score 0.9887) — an in-silico prediction, not a clinical call.

CIT p.Asp230Val

c.689A>T · rs886037894 · VCV254136

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9887 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly 17, primary, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.9887	likely pathogenic ✓ concordant with ClinVar · top 7% in CIT
REVEL	0.823	moderately pathogenic-leaning
SaProt	LLR -13.71	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 91 kb · p 0.38 · regional, not allelic
Overall
CADD	32.0	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.Asp230Val
Coding: c.689A>T
MANE Select: NM_001206999
dbSNP: rs886037894
Type: single nucleotide variant
Location: chr12:119832835 (GRCh38)
Gene constraint: LOEUF 0.353 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.75
Residue 230: the protein kinase domain; a UniProt-annotated variant site (in mcph17; impairs kinase activity; exhibits abnormal mitotic cytokinesis; exhibits multipolar spindles; increases the neurons apoptotic process)

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

Disease context

microcephaly 17, primary, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CIT p.Asp230= Benign ★★ same residue
CIT p.Arg220Ter Pathogenic ★★ same condition
CIT p.Ala1144Thr Uncertain significance ★★ ⚠ same condition
CIT p.Ala244Val Uncertain significance ★★ ⚠ same condition
CIT p.Arg1633Cys Uncertain significance ★★ ⚠ same condition
CIT p.Arg23Trp Uncertain significance ★★ ⚠ same condition
CIT p.Arg696Cys Uncertain significance ★★ same condition
CIT p.Asn1301Ser 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-asp230val (accessed [today's date]).

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