Is ALMS1 p.Glu22= (c.66G>A) pathogenic?

ALMS1 p.Glu22= (c.66G>A) is classified Likely benign in ALMS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-05-27). Very rare (popmax 0.00162%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Glu22= (c.66G>A)?

ALMS1 p.Glu22= (c.66G>A) is associated with Cardiovascular phenotype, Alstrom syndrome (ClinVar).

How common is ALMS1 p.Glu22= (c.66G>A) in the general population?

ALMS1 p.Glu22= (c.66G>A) is very rare (popmax 0.00162%, nfe) (gnomAD).

ALMS1 p.Glu22=

c.66G>A · rs1574423753 · VCV917604

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00162%, nfe)

Conditions

Cardiovascular phenotype

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 -0.093	GERP -1.9
Overall
CADD	4.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00162% European (non-Finnish) · 12/740,990 alleles

Filtering AF 0.000863% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000682%

Overall 0.00137% 13/947,878 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00162%	61,749
African / African-American	0.00157%	63,684

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.Glu22=
Coding: c.66G>A
MANE Select: NM_001378454
dbSNP: rs1574423753
Type: single nucleotide variant
Location: chr2:73385934 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 22: the 'disordered' region

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.Glu22_Glu23insLys Conflicting classifications of pathogenicity ★ same residue
ALMS1 p.Glu22_Glu23insLysGlu Uncertain significance ★ same residue
ALMS1 p.Glu22_Glu28dup Uncertain significance ★ same residue
ALMS1 p.Glu22_Glu29del Conflicting classifications of pathogenicity ★ 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

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-glu22 (accessed [today's date]).

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