Is DCDC2 p.His394fs (c.1181dup) pathogenic?

DCDC2 p.His394fs (c.1181dup) is classified Uncertain significance in DCDC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). Very rare (popmax 0.000508%, nfe).

How common is DCDC2 p.His394fs (c.1181dup) in the general population?

DCDC2 p.His394fs (c.1181dup) is very rare (popmax 0.000508%, nfe) (gnomAD).

DCDC2 p.His394fs

c.1181dup · rs1561878742 · VCV591519

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000508%, nfe)

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 -0.72	GERP 1.6

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000508% European (non-Finnish) · 6/1,180,034 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,614,154 alleles · very rare exomes 6/1,461,888 · genomes 0/152,266 · joint denominator

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.His394fs
Coding: c.1181dup
MANE Select: NM_016356
dbSNP: rs1561878742
Type: Duplication
Location: chr6:24178474 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 394: a UniProt-annotated variant site (in nsc); the 'disordered' region

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

Similar variants

DCDC2 p.Ala324fs Pathogenic/Likely pathogenic ★★ same type
DCDC2 p.Ile177fs Pathogenic ★★ same type
DCDC2 c.349-16dup Benign/Likely benign ★★ same type
DCDC2 p.Asn98fs Pathogenic ★ same type
DCDC2 p.Val184fs Likely pathogenic ★ same type
DCDC2 c.760-16dup Uncertain significance ★ same type
DCDC2 c.1023+154dup Benign ★ same type
DCDC2 c.349-264_349-262dup Benign ★ 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/dcdc2-p-his394fs (accessed [today's date]).

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