Is DCX p.Leu97Val (c.289C>G) pathogenic?

DCX p.Leu97Val (c.289C>G) is classified Likely pathogenic in DCX (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.9749); Absent from gnomAD v4.1; Associated with lissencephaly spectrum disorders.

What condition is associated with DCX p.Leu97Val (c.289C>G)?

DCX p.Leu97Val (c.289C>G) is associated with lissencephaly spectrum disorders (ClinVar).

How common is DCX p.Leu97Val (c.289C>G) in the general population?

DCX p.Leu97Val (c.289C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Leu97Val (c.289C>G)?

AlphaMissense predicts likely pathogenic (score 0.9749) — an in-silico prediction, not a clinical call.

DCX p.Leu97Val

c.289C>G · rs1928574753 · VCV996565

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9749 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

lissencephaly spectrum disorders

Computational evidence

Protein change
AlphaMissense	0.9749	likely pathogenic ✓ concordant with ClinVar
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -12.19	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 0.36, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	24.6	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: DCX
Protein: p.Leu97Val
Coding: c.289C>G
MANE Select: NM_001195553
dbSNP: rs1928574753
Type: single nucleotide variant
Location: chrX:111410110 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 97: the doublecortin 1 domain; a UniProt-annotated variant site (in sbhx)

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

Disease context

lissencephaly spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCX p.Leu97Arg Pathogenic ★ same residue
DCX p.Arg303Ter Pathogenic ★★ same condition
DCX p.Arg78Leu Pathogenic ★★ same condition
DCX p.Arg303Gln Conflicting classifications of pathogenicity ★ same condition
DCX c.364+1G>A Likely pathogenic ★★ same type
DCX c.705+1G>A Pathogenic ★★ same type
DCX c.706-2A>G Pathogenic ★★ same type
DCX c.809-1G>A Pathogenic/Likely pathogenic ★★ 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/dcx-p-leu97val (accessed [today's date]).

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