Is DCX p.Pro191Thr (c.571C>A) pathogenic?

DCX p.Pro191Thr (c.571C>A) is classified Likely pathogenic in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2013-02-08). AlphaMissense: likely pathogenic (0.9995); Absent from gnomAD v4.1; Associated with Ectopic tissue.

What condition is associated with DCX p.Pro191Thr (c.571C>A)?

DCX p.Pro191Thr (c.571C>A) is associated with Ectopic tissue (ClinVar).

How common is DCX p.Pro191Thr (c.571C>A) in the general population?

DCX p.Pro191Thr (c.571C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCX p.Pro191Thr (c.571C>A)?

AlphaMissense predicts likely pathogenic (score 0.9995) — an in-silico prediction, not a clinical call.

DCX p.Pro191Thr

c.571C>A · rs587783565 · VCV158480

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9995 · 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	0.9995	likely pathogenic ✓ concordant with ClinVar · top 6% in DCX
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -12.72	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.31	constrained · MANE · 77 kb · p 4.4e-24 · regional, not allelic
Overall
CADD	25.7	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.Pro191Thr
Coding: c.571C>A
MANE Select: NM_001195553
dbSNP: rs587783565
Type: single nucleotide variant
Location: chrX:111401124 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 191: the doublecortin 2 domain; a UniProt-annotated variant site (in sbhx); a β-strand

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.Pro191Arg Pathogenic ★★ same residue
DCX p.Pro191Leu Likely pathogenic ★ same residue
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

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-pro191thr (accessed [today's date]).

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