Is ALMS1 p.Arg2588= (c.7764G>A) pathogenic?

ALMS1 p.Arg2588= (c.7764G>A) is classified Likely benign in ALMS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-22). Very rare (popmax 0.004%, afr); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Arg2588= (c.7764G>A)?

ALMS1 p.Arg2588= (c.7764G>A) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Arg2588= (c.7764G>A) in the general population?

ALMS1 p.Arg2588= (c.7764G>A) is very rare (popmax 0.004%, afr) (gnomAD).

How is Alström syndrome inherited?

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

ALMS1 p.Arg2588=

c.7764G>A · rs565248215 · VCV1093685

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 1.6	GERP -0.008, phastCons 1
Overall
CADD	4.852	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,022 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.00248% 40/1,614,078 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,007
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)	0.00297%	33,715

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.Arg2588=
Coding: c.7764G>A
MANE Select: NM_001378454
dbSNP: rs565248215
Type: single nucleotide variant
Location: chr2:73489723 (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.Arg2588Gln Uncertain significance ★★ ⚠ same residue
ALMS1 p.Arg2588Trp 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
ALMS1 c.11668+1G>T Pathogenic/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-arg2588 (accessed [today's date]).

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