Is ALMS1 p.Val41= (c.123G>C) pathogenic?

ALMS1 p.Val41= (c.123G>C) is classified Likely benign in ALMS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-03). Very rare (popmax 0.00244%, nfe); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Val41= (c.123G>C)?

ALMS1 p.Val41= (c.123G>C) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Val41= (c.123G>C) in the general population?

ALMS1 p.Val41= (c.123G>C) is very rare (popmax 0.00244%, nfe) (gnomAD).

How is Alström syndrome inherited?

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

ALMS1 p.Val41=

c.123G>C · rs1233161159 · VCV1765108

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00244%, nfe)

Conditions

Alstrom syndrome

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 0.33	GERP -0.069, phastCons 0.05
Overall
CADD	5.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00244% European (non-Finnish) · 28/1,147,726 alleles

Filtering AF 0.00169% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00146%

Overall 0.00187% 29/1,552,214 alleles · very rare exomes 26/1,400,056 · genomes 3/152,158 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00244%	40,990
Remaining individualsnot grpmax-eligible	0.00166%	60,210

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.Val41=
Coding: c.123G>C
MANE Select: NM_001378454
dbSNP: rs1233161159
Type: single nucleotide variant
Location: chr2:73385991 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 41: 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.Val41Ala Uncertain significance ★★ ⚠ same residue
ALMS1 p.Val41Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ALMS1 p.Val41Met 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

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-val41 (accessed [today's date]).

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