Is DCDC2 p.Glu386fs (c.1155del) pathogenic?

DCDC2 p.Glu386fs (c.1155del) is classified Likely pathogenic in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-14). Very rare (popmax 8.47e-05%, nfe); Associated with DCDC2-related disorder.

What condition is associated with DCDC2 p.Glu386fs (c.1155del)?

DCDC2 p.Glu386fs (c.1155del) is associated with DCDC2-related disorder (ClinVar).

How common is DCDC2 p.Glu386fs (c.1155del) in the general population?

DCDC2 p.Glu386fs (c.1155del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

DCDC2 p.Glu386fs

c.1155del · rs962387857 · VCV2629455

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

DCDC2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.004	GERP -0.3
Overall
CADD	10.36	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,048 alleles

Overall 0.000124% 2/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
European (non-Finnish)grpmax	8.47e-05%	1,180,048

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: DCDC2
Protein: p.Glu386fs
Coding: c.1155del
MANE Select: NM_016356
dbSNP: rs962387857
Type: Deletion
Location: chr6:24178501 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 386: a UniProt-annotated variant site (in nsc); the 'disordered' region

Full DCDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DCDC2-related disorder

Similar variants

DCDC2 p.Val113fs Likely pathogenic ★ same condition
DCDC2 c.705-2A>G Pathogenic ★★ same condition
DCDC2 c.557+1G>T Pathogenic ★ same condition
DCDC2 p.Gln448Lys Uncertain significance ★ ⚠ same condition
DCDC2 p.Gln417Ter Likely pathogenic same condition
DCDC2 p.Gly368Glu Uncertain significance ⚠ same condition
DCDC2 p.Lys249Gln Uncertain significance ⚠ same condition
DCDC2 c.1326+6T>G Likely benign 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/dcdc2-p-glu386fs (accessed [today's date]).

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