Is ALMS1 p.Pro3Ser (c.7C>T) pathogenic?

ALMS1 p.Pro3Ser (c.7C>T) is classified Uncertain significance in ALMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-12). AlphaMissense: likely pathogenic (0.7493); Ultra-rare (popmax 0.0103%, sas); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Pro3Ser (c.7C>T)?

ALMS1 p.Pro3Ser (c.7C>T) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Pro3Ser (c.7C>T) in the general population?

ALMS1 p.Pro3Ser (c.7C>T) is ultra-rare (popmax 0.0103%, sas) (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.Pro3Ser (c.7C>T)?

AlphaMissense predicts likely pathogenic (score 0.7493) — an in-silico prediction, not a clinical call.

ALMS1 p.Pro3Ser

c.7C>T · rs1053425100 · VCV2155414

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7493 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, sas)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Alstrom syndrome

Computational evidence

Protein change
AlphaMissense	0.7493	likely pathogenic · top 3% in ALMS1
REVEL	0.052	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 5	GERP 1.8, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	23.0	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 0.0103% South Asian · 7/68,076 alleles

Filtering AF 0.00476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00334%

Overall 0.00104% 8/768,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0103%	9,725
Remaining individualsnot grpmax-eligible	0.00289%	34,560

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.Pro3Ser
Coding: c.7C>T
MANE Select: NM_001378454
dbSNP: rs1053425100
Type: single nucleotide variant
Location: chr2:73385875 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 3: the 'disordered' region

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.Pro3Leu Uncertain significance ★★ ⚠ same residue
ALMS1 p.Pro3= Likely benign ★ 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-pro3ser (accessed [today's date]).

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