Is DCLRE1C p.Pro413fs (c.1238del) pathogenic?

DCLRE1C p.Pro413fs (c.1238del) is classified Pathogenic/Likely pathogenic in DCLRE1C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-07). Absent from gnomAD; Associated with Omenn syndrome.

What condition is associated with DCLRE1C p.Pro413fs (c.1238del)?

DCLRE1C p.Pro413fs (c.1238del) is associated with Omenn syndrome, severe combined immunodeficiency due to DCLRE1C deficiency, severe combined immunodeficiency (ClinVar).

How common is DCLRE1C p.Pro413fs (c.1238del) in the general population?

DCLRE1C p.Pro413fs (c.1238del) is absent from gnomAD (gnomAD).

How is Omenn syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DCLRE1C p.Pro413fs

c.1238del · rs2491636150 · VCV2674744

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Omenn syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (14 of 14) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.86	phastCons 0.27

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: DCLRE1C
Protein: p.Pro413fs
Coding: c.1238del
MANE Select: NM_001033855
dbSNP: rs2491636150
Type: Deletion
Location: chr10:14909249 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 14 PDB

Full DCLRE1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Omenn syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: severe combined immunodeficiency due to DCLRE1C deficiency severe combined immunodeficiency

For Omenn syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DCLRE1C c.780+1del Pathogenic/Likely pathogenic ★★ same condition
DCLRE1C p.Asp451fs Pathogenic ★★ same condition
DCLRE1C p.Asp556fs Pathogenic/Likely pathogenic ★★ same condition
DCLRE1C p.Gly154fs Pathogenic/Likely pathogenic ★★ same condition
DCLRE1C p.Gly224fs Pathogenic/Likely pathogenic ★★ same condition
DCLRE1C p.Ile543fs Pathogenic/Likely pathogenic ★★ same condition
DCLRE1C p.Lys368fs Pathogenic/Likely pathogenic ★★ same condition
DCLRE1C p.Lys481fs Pathogenic/Likely pathogenic ★★ 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/dclre1c-p-pro413fs (accessed [today's date]).

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