Is ALMS1 p.Pro89Ser (c.265C>T) pathogenic?

ALMS1 p.Pro89Ser (c.265C>T) is classified Uncertain significance in ALMS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-26). AlphaMissense: likely benign (0.1414); No allele count reported in gnomAD v4.1 (AN 1,566,056); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Pro89Ser (c.265C>T)?

ALMS1 p.Pro89Ser (c.265C>T) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Pro89Ser (c.265C>T) in the general population?

ALMS1 p.Pro89Ser (c.265C>T) is no allele count reported in gnomAD v4.1 (AN 1,566,056) (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.Pro89Ser (c.265C>T)?

AlphaMissense predicts likely benign (score 0.1414) — an in-silico prediction, not a clinical call.

ALMS1 p.Pro89Ser

c.265C>T · rs956834448 · VCV1033322

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1414 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,566,056)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Alstrom syndrome

Computational evidence

Protein change
AlphaMissense	0.1414	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.58	GERP -0.79
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	8.005	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,566,056). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ALMS1
Protein: p.Pro89Ser
Coding: c.265C>T
MANE Select: NM_001378454
dbSNP: rs956834448
Type: single nucleotide variant
Location: chr2:73386133 (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.Pro89Leu 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-pro89ser (accessed [today's date]).

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