Is ALMS1 p.Asp845= (c.2535C>T) pathogenic?

ALMS1 p.Asp845= (c.2535C>T) is classified Benign in ALMS1 (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-02-04). Common (popmax 11.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Asp845= (c.2535C>T)?

ALMS1 p.Asp845= (c.2535C>T) is associated with Cardiovascular phenotype, Alstrom syndrome (ClinVar).

ALMS1 p.Asp845=

Q: How common is ALMS1 p.Asp845= (c.2535C>T) in the general population?

ALMS1 p.Asp845= (c.2535C>T) is common (popmax 11.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2535C>T · rs77517267 · VCV387348

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Common

common (popmax 11.6%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -3
Overall
CADD	2.113	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.6% African / African-American · 8,694/75,026 alleles

Filtering AF 11.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.3%

Overall 0.627% 10,114/1,614,074 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.6%	9
Remaining individualsnot grpmax-eligible	0.787%	127
Admixed American	0.77%	130
Middle Eastern	0.693%	144
European (non-Finnish)	0.0334%	2,995
South Asian	0.0318%	3,141
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,602

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.Asp845=
Coding: c.2535C>T
MANE Select: NM_001378454
dbSNP: rs77517267
Type: single nucleotide variant
Location: chr2:73449062 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 845: 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

Disease context

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

Also linked: Alstrom syndrome

Similar variants

ALMS1 p.Asp845Glu 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
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-asp845 (accessed [today's date]).

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