Is IGFALS p.Ser112fs (c.334_346delinsCCTGCT) pathogenic?

IGFALS p.Ser112fs (c.334346delinsCCTGCT) is classified Likely pathogenic in IGFALS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-21). Associated with short stature due to primary acid-labile subunit deficiency.

What condition is associated with IGFALS p.Ser112fs (c.334_346delinsCCTGCT)?

IGFALS p.Ser112fs (c.334_346delinsCCTGCT) is associated with short stature due to primary acid-labile subunit deficiency (ClinVar).

IGFALS p.Ser112fs

Q: How is Short stature due to primary acid-labile subunit deficiency inherited?

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

c.334_346delinsCCTGCT · VCV3578693

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

short stature due to primary acid-labile subunit deficiency

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 (2 of 2) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP -3.2, phastCons 0.48

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

Variant & gene context

Gene: IGFALS
Protein: p.Ser112fs
Coding: c.334_346delinsCCTGCT
MANE Select: NM_004970
Type: Indel
Location: chr16:1792072 (GRCh38)
Gene constraint: LOEUF 1.908 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 91.13 · 1 PDB

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

Disease context

short stature due to primary acid-labile subunit deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Short stature due to primary acid-labile subunit deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

IGFALS p.Leu290fs Likely pathogenic ★ same condition
IGFALS p.Asn580_Ile581delinsIleThr Uncertain significance ★ same condition
IGFALS p.Asn276Ser Likely pathogenic ★★ same condition
IGFALS p.Ala147Thr Uncertain significance ★★ ⚠ same condition
IGFALS p.Ala258Val Uncertain significance ★★ ⚠ same condition
IGFALS p.Ala551Thr Uncertain significance ★★ ⚠ same condition
IGFALS p.Arg306Gln Uncertain significance ★★ ⚠ same condition
IGFALS p.Arg493His Uncertain significance ★★ ⚠ 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/igfals-p-ser112fs (accessed [today's date]).

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