Is UNC13D p.Ser358fs (c.1072dup) pathogenic?

UNC13D p.Ser358fs (c.1072dup) is classified Pathogenic in UNC13D (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-17). No gnomAD frequency available for this variant; Associated with familial hemophagocytic lymphohistiocytosis 3.

What condition is associated with UNC13D p.Ser358fs (c.1072dup)?

UNC13D p.Ser358fs (c.1072dup) is associated with familial hemophagocytic lymphohistiocytosis 3 (ClinVar).

How common is UNC13D p.Ser358fs (c.1072dup) in the general population?

UNC13D p.Ser358fs (c.1072dup) is no gnomAD frequency available for this variant (gnomAD).

How is Familial hemophagocytic lymphohistiocytosis inherited?

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

UNC13D p.Ser358fs

c.1072dup · rs2143883327 · VCV1455815

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

familial hemophagocytic lymphohistiocytosis 3

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 13 of 32
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	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: UNC13D
Protein: p.Ser358fs
Coding: c.1072dup
MANE Select: NM_199242
dbSNP: rs2143883327
Type: Duplication
Location: chr17:75836901 (GRCh38)
Gene constraint: LOEUF 0.923 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.04 · 1 PDB
Residue 358: the 'interaction with rab27a' region

Full UNC13D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

familial hemophagocytic lymphohistiocytosis 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Familial hemophagocytic lymphohistiocytosis (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Infancy
Prevalence: 1-9 / 100 000 (Sweden)

Similar variants

UNC13D p.Ser358Gly Likely benign ★ ⚠ same residue
UNC13D p.Arg27fs Pathogenic/Likely pathogenic ★★ same condition
UNC13D p.Arg411fs Pathogenic/Likely pathogenic ★★ same condition
UNC13D c.2091+2_2091+3dup Uncertain significance ★★ same condition
UNC13D c.2448-8dup Benign/Likely benign ★★ same condition
UNC13D p.Arg172fs Likely pathogenic ★ same condition
UNC13D p.Arg293fs Pathogenic ★ same condition
UNC13D p.Gln142fs 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/unc13d-p-ser358fs (accessed [today's date]).

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