Is ALG1 p.Cys385fs (c.1149_1150delinsT) pathogenic?

ALG1 p.Cys385fs (c.11491150delinsT) is classified Likely pathogenic in ALG1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-06-26). Associated with ALG1-related disorder.

What condition is associated with ALG1 p.Cys385fs (c.1149_1150delinsT)?

ALG1 p.Cys385fs (c.1149_1150delinsT) is associated with ALG1-related disorder (ClinVar).

ALG1 p.Cys385fs

c.1149_1150delinsT · VCV3347363

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

ALG1-related disorder

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 11 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -5.6	GERP -3.3
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.

Variant & gene context

Gene: ALG1
Protein: p.Cys385fs
Coding: c.1149_1150delinsT
MANE Select: NM_019109
Type: Indel
Location: chr16:5082635 (GRCh38)
Gene constraint: LOEUF 1.419 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.24

Full ALG1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ALG1-related disorder

Similar variants

ALG1 p.Ser258Leu Pathogenic/Likely pathogenic ★★ ⚠ same condition
ALG1 p.Tyr113Ter Pathogenic/Likely pathogenic ★★ same condition
ALG1 p.Arg247His Likely pathogenic ★ same condition
ALG1 c.1187+3A>G Conflicting classifications of pathogenicity ★ same condition
ALG1 p.Val39fs Conflicting classifications of pathogenicity ★ same condition
ALG1 c.*5T>C Likely benign same condition
ALG1 p.Cys390= Likely benign same condition
ALG1 p.Glu275= Likely benign 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/alg1-p-cys385fs (accessed [today's date]).

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