Is SBDS p.Val36fs (c.107del) pathogenic?

SBDS p.Val36fs (c.107del) is classified Pathogenic in SBDS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-11). Very rare (popmax 0.000254%, nfe); Associated with Shwachman-Diamond syndrome 1.

What condition is associated with SBDS p.Val36fs (c.107del)?

SBDS p.Val36fs (c.107del) is associated with Shwachman-Diamond syndrome 1, aplastic anemia (ClinVar).

How common is SBDS p.Val36fs (c.107del) in the general population?

SBDS p.Val36fs (c.107del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Shwachman-Diamond syndrome inherited?

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

SBDS p.Val36fs

c.107del · rs2536932418 · VCV2678592

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Shwachman-Diamond syndrome 1

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 1 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -3.6, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,998 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,998 alleles · very rare exomes 3/1,461,638 · genomes 0/152,360 · 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: SBDS
Protein: p.Val36fs
Coding: c.107del
MANE Select: NM_016038
dbSNP: rs2536932418
Type: Deletion
Location: chr7:66995311 (GRCh38)
Gene constraint: LOEUF 1.08 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.97 · 6 PDB
Residue 36: an α-helix

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

Disease context

Shwachman-Diamond syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: aplastic anemia

For Shwachman-Diamond syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Italy)

Similar variants

SBDS p.Ser41fs Pathogenic ★★ same condition
SBDS p.Thr5fs Pathogenic/Likely pathogenic ★★ same condition
SBDS p.Thr7fs Pathogenic ★★ same condition
SBDS p.Val36Ala Uncertain significance ★★ ⚠ same residue
SBDS c.129-71_140del Likely pathogenic ★ same condition
SBDS c.625-1delG Pathogenic ★ same condition
SBDS p.Arg175fs Likely pathogenic ★ same condition
SBDS p.Lys189fs 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/sbds-p-val36fs (accessed [today's date]).

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