Is DCC p.Ser1406fs (c.4211_4215dup) pathogenic?

DCC p.Ser1406fs (c.42114215dup) is classified Uncertain significance in DCC (ClinVar, Single submitter, 2 submitters; last evaluated 2024-02-14). Absent from gnomAD.

How common is DCC p.Ser1406fs (c.4211_4215dup) in the general population?

DCC p.Ser1406fs (c.4211_4215dup) is absent from gnomAD (gnomAD).

DCC p.Ser1406fs

c.4211_4215dup · rs2511519166 · VCV3028994

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon within the last 50 nt of the penultimate exon (28 of 29, 46 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DCC
Protein: p.Ser1406fs
Coding: c.4211_4215dup
MANE Select: NM_005215
dbSNP: rs2511519166
Type: Duplication
Location: chr18:53526713 (GRCh38)
Gene constraint: LOEUF 0.414 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.60 · 9 PDB
Residue 1406: the 'disordered' region; a UniProt-annotated variant site (in mrmv1; likely pathogenic)

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

Similar variants

DCC p.Ala713fs Pathogenic ★ same type
DCC p.Cys740fs Likely pathogenic ★ same type
DCC p.Ile1000fs Likely pathogenic ★ same type
DCC c.4111+4_4111+8dup Uncertain significance ★ same type
DCC p.Asn925fs Pathogenic same type
DCC p.Gly31fs Likely pathogenic same type
DCC p.Val191fs Pathogenic same type
DCC p.Pro1351fs Uncertain significance 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/dcc-p-ser1406fs (accessed [today's date]).

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