Is DCX p.Ser339Asn (c.1016G>A) pathogenic?

DCX p.Ser339Asn (c.1016G>A) is classified Uncertain significance in DCX (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-30). AlphaMissense: likely pathogenic (0.8653); Very rare (popmax 0.00217%, amr).

How common is DCX p.Ser339Asn (c.1016G>A) in the general population?

DCX p.Ser339Asn (c.1016G>A) is very rare (popmax 0.00217%, amr) (gnomAD).

What do computational predictors say about DCX p.Ser339Asn (c.1016G>A)?

AlphaMissense predicts likely pathogenic (score 0.8653) — an in-silico prediction, not a clinical call.

DCX p.Ser339Asn

c.1016G>A · rs751019908 · VCV3011839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00217%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8653	likely pathogenic
REVEL	0.252	benign-leaning
SaProt	LLR -8.64	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 31 kb · p 0.075 · 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

Grpmax group 0.00217% Admixed American · 1/46,048 alleles

Overall 9.11e-05% 1/1,098,186 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.Ser339Asn
Coding: c.1016G>A
MANE Select: NM_001195553
dbSNP: rs751019908
Type: single nucleotide variant
Location: chrX:111312667 (GRCh38)
Structure: AlphaFold pLDDT 67.19 · 14 PDB
Residue 339: a modified residue (phosphoserine; by cdk5); a modified residue (phosphoserine; by mapk); the 'disordered' region

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

Similar variants

DCX p.Ser339Arg Uncertain significance ★ ⚠ same residue
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

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-ser339asn (accessed [today's date]).

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