Is ALMS1 p.Arg2159= (c.6477A>G) pathogenic?

ALMS1 p.Arg2159= (c.6477A>G) is classified Likely benign in ALMS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-22). Very rare (popmax 8.48e-05%, nfe); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Arg2159= (c.6477A>G)?

ALMS1 p.Arg2159= (c.6477A>G) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Arg2159= (c.6477A>G) in the general population?

ALMS1 p.Arg2159= (c.6477A>G) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is Alström syndrome inherited?

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

ALMS1 p.Arg2159=

c.6477A>G · rs772943318 · VCV1753765

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

Alstrom syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP -3.4, phastCons 0.83
Overall
CADD	3.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,654 alleles

Overall 6.85e-05% 1/1,460,620 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.Arg2159=
Coding: c.6477A>G
MANE Select: NM_001378454
dbSNP: rs772943318
Type: single nucleotide variant
Location: chr2:73453004 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2159: 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.Arg2159Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
ALMS1 p.Arg2159fs Pathogenic ★ same residue
ALMS1 p.Arg2159Gly Uncertain significance ★★ ⚠ same residue
ALMS1 c.10079-1G>C Likely pathogenic ★★ same condition
ALMS1 c.10214-2A>G Likely pathogenic ★★ same condition
ALMS1 c.10384+1G>A Likely pathogenic ★★ same condition
ALMS1 c.10385-2A>G Pathogenic ★★ same condition
ALMS1 c.11547+3A>T Likely 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-arg2159 (accessed [today's date]).

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