Is DCX p.Leu91Pro (c.272T>C) pathogenic?

DCX p.Leu91Pro (c.272T>C) is classified Pathogenic in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). AlphaMissense: likely pathogenic (0.9999); Absent from gnomAD v4.1; Associated with Ectopic tissue.

What condition is associated with DCX p.Leu91Pro (c.272T>C)?

DCX p.Leu91Pro (c.272T>C) is associated with Ectopic tissue (ClinVar).

How common is DCX p.Leu91Pro (c.272T>C) in the general population?

DCX p.Leu91Pro (c.272T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Leu91Pro (c.272T>C)?

AlphaMissense predicts likely pathogenic (score 0.9999) — an in-silico prediction, not a clinical call.

DCX p.Leu91Pro

c.272T>C · rs587783536 · VCV158446

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9999 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ectopic tissue

Computational evidence

Protein change
AlphaMissense	0.9999	likely pathogenic ✓ concordant with ClinVar · top 6% in DCX
REVEL	0.959	strongly pathogenic-leaning
SaProt	LLR -13.05	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 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	28.5	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: DCX
Protein: p.Leu91Pro
Coding: c.272T>C
MANE Select: NM_001195553
dbSNP: rs587783536
Type: single nucleotide variant
Location: chrX:111410127 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 91: the doublecortin 1 domain; an α-helix

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

Disease context

Ectopic tissue — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCX p.Ala204Asp Pathogenic ★★ same condition
DCX p.Ala251Ser Pathogenic ★★ same condition
DCX p.Arg186Cys Pathogenic ★★ same condition
DCX p.Arg192Trp Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg196Cys Pathogenic ★★ same condition
DCX p.Arg59His Pathogenic/Likely pathogenic ★★ same condition
DCX p.Arg78Cys Pathogenic ★★ same condition
DCX p.Arg78Leu Pathogenic ★★ 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/dcx-p-leu91pro (accessed [today's date]).

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