Is ALMS1 p.Gln519fs (c.1557del) pathogenic?

ALMS1 p.Gln519fs (c.1557del) is classified Pathogenic in ALMS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-18). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Gln519fs (c.1557del)?

ALMS1 p.Gln519fs (c.1557del) is associated with Cardiovascular phenotype, Alstrom syndrome (ClinVar).

How common is ALMS1 p.Gln519fs (c.1557del) in the general population?

ALMS1 p.Gln519fs (c.1557del) is absent from gnomAD (gnomAD).

ALMS1 p.Gln519fs

c.1557del · rs1553403262 · VCV551253

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

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 1.8	GERP -0.69, phastCons 0.54

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: ALMS1
Protein: p.Gln519fs
Coding: c.1557del
MANE Select: NM_001378454
dbSNP: rs1553403262
Type: Deletion
Location: chr2:73448084 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Alstrom syndrome

Similar variants

ALMS1 p.Gln519= Likely benign ★★ same residue
ALMS1 p.Gln519Arg Uncertain significance ★ ⚠ 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

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-gln519fs (accessed [today's date]).

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