Is ALMS1 p.Ala82Pro (c.244G>C) pathogenic?

ALMS1 p.Ala82Pro (c.244G>C) is classified Uncertain significance in ALMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-25). AlphaMissense: likely pathogenic (0.814); Ultra-rare (popmax 0.0116%, eas); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Ala82Pro (c.244G>C)?

ALMS1 p.Ala82Pro (c.244G>C) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Ala82Pro (c.244G>C) in the general population?

ALMS1 p.Ala82Pro (c.244G>C) is ultra-rare (popmax 0.0116%, eas) (gnomAD).

How is Alström syndrome inherited?

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

What do computational predictors say about ALMS1 p.Ala82Pro (c.244G>C)?

AlphaMissense predicts likely pathogenic (score 0.814) — an in-silico prediction, not a clinical call.

ALMS1 p.Ala82Pro

c.244G>C · rs1453391868 · VCV1385506

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.814 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0116%, eas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Alstrom syndrome

Computational evidence

Protein change
AlphaMissense	0.814	likely pathogenic · top 2% in ALMS1
REVEL	0.139	moderately benign-leaning
⇒ AlphaMissense calls this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0116% East Asian · 5/43,128 alleles

Filtering AF 0.00449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00295%

Overall 0.000316% 5/1,584,672 alleles · ultra-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.Ala82Pro
Coding: c.244G>C
MANE Select: NM_001378454
dbSNP: rs1453391868
Type: single nucleotide variant
Location: chr2:73386112 (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.Ala82Val 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-ala82pro (accessed [today's date]).

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