Is ALMS1 p.Asp287= (c.861C>T) pathogenic?

ALMS1 p.Asp287= (c.861C>T) is classified Conflicting classifications of pathogenicity in ALMS1 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-14). Ultra-rare (popmax 0.0452%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Asp287= (c.861C>T)?

ALMS1 p.Asp287= (c.861C>T) is associated with Cardiovascular phenotype, Alstrom syndrome (ClinVar).

How common is ALMS1 p.Asp287= (c.861C>T) in the general population?

ALMS1 p.Asp287= (c.861C>T) is ultra-rare (popmax 0.0452%, amr) (gnomAD).

ALMS1 p.Asp287=

c.861C>T · rs377281121 · VCV529405

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0452%, amr)

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 -0.49	GERP -2.2, phastCons 0.006
Overall
CADD	3.155	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0452% Admixed American · 27/59,736 alleles

Filtering AF 0.0318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0274%

Overall 0.023% 370/1,611,382 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0452%	2,212
European (non-Finnish)	0.0285%	3,507
Ashkenazi Jewishnot grpmax-eligible	0.0169%	5,903
Remaining individualsnot grpmax-eligible	0.00321%	31,178

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.Asp287=
Coding: c.861C>T
MANE Select: NM_001378454
dbSNP: rs377281121
Type: single nucleotide variant
Location: chr2:73424526 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Alstrom syndrome

Similar variants

ALMS1 p.Asp287Gly 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
ALMS1 c.11669-1G>A 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-asp287 (accessed [today's date]).

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