Is ALMS1 p.Pro558fs (c.1671del) pathogenic?

ALMS1 p.Pro558fs (c.1671del) is classified Likely pathogenic in ALMS1 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD.

How common is ALMS1 p.Pro558fs (c.1671del) in the general population?

ALMS1 p.Pro558fs (c.1671del) is absent from gnomAD (gnomAD).

ALMS1 p.Pro558fs

c.1671del · rs786205633 · VCV191303

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 -3.5
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

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.Pro558fs
Coding: c.1671del
MANE Select: NM_001378454
dbSNP: rs786205633
Type: Deletion
Location: chr2:73448197 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 558: the '34 x 47 aa approximate tandem repeat' region; the 'disordered' region

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

Similar variants

ALMS1 p.Pro558= Likely benign ★ same residue
ALMS1 c.1432+2_1432+15del Likely pathogenic ★★ same type
ALMS1 c.9782-1269_9859del Likely pathogenic ★★ same type
ALMS1 p.Ala1083fs Pathogenic ★★ same type
ALMS1 p.Ala1515fs Pathogenic/Likely pathogenic ★★ same type
ALMS1 p.Ala3307fs Pathogenic/Likely pathogenic ★★ same type
ALMS1 p.Ala50fs Pathogenic ★★ same type
ALMS1 p.Arg1417fs Pathogenic ★★ same type

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-pro558fs (accessed [today's date]).

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