Is ALMS1 p.Pro3348fs (c.10043del) pathogenic?

ALMS1 p.Pro3348fs (c.10043del) is classified Likely pathogenic in ALMS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-04-10). Very rare (popmax 8.47e-05%, nfe); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Pro3348fs (c.10043del)?

ALMS1 p.Pro3348fs (c.10043del) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Pro3348fs (c.10043del) in the general population?

ALMS1 p.Pro3348fs (c.10043del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Alström syndrome inherited?

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

ALMS1 p.Pro3348fs

c.10043del · rs1553416233 · VCV557705

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 13 of 23
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.44	GERP -2.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,006 alleles

Overall 6.84e-05% 1/1,461,848 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.Pro3348fs
Coding: c.10043del
MANE Select: NM_001378454
dbSNP: rs1553416233
Type: Deletion
Location: chr2:73550401 (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

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.Pro3348Ser 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
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-pro3348fs (accessed [today's date]).

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