Is ALMS1 p.Gln1908His (c.5724G>C) pathogenic?

ALMS1 p.Gln1908His (c.5724G>C) is classified Conflicting classifications of pathogenicity in ALMS1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2025-08-27). AlphaMissense: likely benign (0.3004); Ultra-rare (popmax 0.0822%, mid); Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Gln1908His (c.5724G>C)?

ALMS1 p.Gln1908His (c.5724G>C) is associated with Cardiovascular phenotype, Alstrom syndrome (ClinVar).

How common is ALMS1 p.Gln1908His (c.5724G>C) in the general population?

ALMS1 p.Gln1908His (c.5724G>C) is ultra-rare (popmax 0.0822%, mid) (gnomAD).

What do computational predictors say about ALMS1 p.Gln1908His (c.5724G>C)?

AlphaMissense predicts likely benign (score 0.3004) — an in-silico prediction, not a clinical call.

ALMS1 p.Gln1908His

c.5724G>C · rs779739318 · VCV459873

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.3004 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0822%, mid)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.3004	likely benign
REVEL	0.032	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.5	GERP 0.14
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	17.3	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 0.0822% Middle Eastern · 5/6,084 alleles

Filtering AF 0.0323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00266% 43/1,613,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0822%	1,217
African / African-American	0.00534%	18,724
European (non-Finnish)	0.00271%	36,875
Admixed American	0.00167%	59,960
Remaining individualsnot grpmax-eligible	0.0016%	62,488

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.Gln1908His
Coding: c.5724G>C
MANE Select: NM_001378454
dbSNP: rs779739318
Type: single nucleotide variant
Location: chr2:73452251 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1908: the '34 x 47 aa approximate tandem repeat' 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.Gln1908Ter Pathogenic ★ 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-gln1908his (accessed [today's date]).

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