Is DCX p.Thr281Pro (c.841A>C) pathogenic?

DCX p.Thr281Pro (c.841A>C) is classified Uncertain significance in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-01). AlphaMissense: likely benign (0.0607); Very rare (popmax 0.00295%, eas).

How common is DCX p.Thr281Pro (c.841A>C) in the general population?

DCX p.Thr281Pro (c.841A>C) is very rare (popmax 0.00295%, eas) (gnomAD).

What do computational predictors say about DCX p.Thr281Pro (c.841A>C)?

AlphaMissense predicts likely benign (score 0.0607) — an in-silico prediction, not a clinical call.

DCX p.Thr281Pro

c.841A>C · VCV4534713

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0607 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00295%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0607	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.07	GERP -0.95, phastCons 0.45
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · regional, not allelic
Overall
CADD	19.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00295% East Asian · 1/33,849 alleles

Overall 9.11e-05% 1/1,097,964 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DCX
Protein: p.Thr281Pro
Coding: c.841A>C
MANE Select: NM_001195553
Type: single nucleotide variant
Location: chrX:111331009 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 281: the 'disordered' region

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

Similar variants

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
DCX p.Ala204Asp Pathogenic ★★ same type
DCX p.Ala251Ser Pathogenic ★★ same type
DCX p.Arg178Cys Pathogenic/Likely pathogenic ★★ same type
DCX p.Arg186Cys 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-thr281pro (accessed [today's date]).

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