Is ALMS1 p.Glu596fs (c.1786del) pathogenic?

ALMS1 p.Glu596fs (c.1786del) is classified Pathogenic in ALMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). Very rare (popmax 0.000254%, nfe); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Glu596fs (c.1786del)?

ALMS1 p.Glu596fs (c.1786del) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Glu596fs (c.1786del) in the general population?

ALMS1 p.Glu596fs (c.1786del) is very rare (popmax 0.000254%, nfe) (gnomAD).

How is Alström syndrome inherited?

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

ALMS1 p.Glu596fs

c.1786del · rs2466092307 · VCV2203097

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Conditions

Alstrom 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	predicted	premature termination codon in exon 8 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.31	GERP -2.2
Region caveats
Repeat context	tandem	CAGATAGTCATCTAACTGAAGAGGCTCTGAAAGTTTCAGCTGTTCCTGGACCAGCTGACCAGAAGACTGGCATACCAACTGTAACCTCTACTTCCTACTCACATAGAGAGAAGCCTAGTATTTTCTACCAACAGGCCTTGC simple repeat · ambiguous alignment · 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) · 3/1,179,946 alleles

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

Overall 0.000205% 3/1,461,784 alleles · very rare

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: ALMS1
Protein: p.Glu596fs
Coding: c.1786del
MANE Select: NM_001378454
dbSNP: rs2466092307
Type: Deletion
Location: chr2:73448313 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 596: the '34 x 47 aa approximate tandem repeat' region

Full ALMS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

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

For Alström syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

ALMS1 p.Glu596Ter Pathogenic ★ same residue
ALMS1 c.1432+2_1432+15del Likely pathogenic ★★ same condition
ALMS1 c.9782-1269_9859del Likely pathogenic ★★ same condition
ALMS1 p.Ala1083fs Pathogenic ★★ same condition
ALMS1 p.Ala1515fs Pathogenic/Likely pathogenic ★★ same condition
ALMS1 p.Ala3307fs Pathogenic/Likely pathogenic ★★ same condition
ALMS1 p.Ala50fs Pathogenic ★★ same condition
ALMS1 p.Arg1417fs 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/alms1-p-glu596fs (accessed [today's date]).

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