Is ALMS1 p.Cys211Ser (c.632G>C) pathogenic?

ALMS1 p.Cys211Ser (c.632G>C) is classified Uncertain significance in ALMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-15). AlphaMissense: likely pathogenic (0.7909); Very rare (popmax 0.00119%, nfe); Associated with Alstrom syndrome.

What condition is associated with ALMS1 p.Cys211Ser (c.632G>C)?

ALMS1 p.Cys211Ser (c.632G>C) is associated with Alstrom syndrome (ClinVar).

How common is ALMS1 p.Cys211Ser (c.632G>C) in the general population?

ALMS1 p.Cys211Ser (c.632G>C) is very rare (popmax 0.00119%, nfe) (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.Cys211Ser (c.632G>C)?

AlphaMissense predicts likely pathogenic (score 0.7909) — an in-silico prediction, not a clinical call.

ALMS1 p.Cys211Ser

c.632G>C · rs770306871 · VCV1943141

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7909 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Alstrom syndrome

Computational evidence

Protein change
AlphaMissense	0.7909	likely pathogenic · top 2% in ALMS1
REVEL	0.157	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 9.5	GERP 0.91, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	20.7	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 0.00119% European (non-Finnish) · 14/1,179,820 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.0044% 71/1,613,754 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0875%	1,143
Remaining individualsnot grpmax-eligible	0.0016%	62,474
European (non-Finnish)grpmax	0.00119%	84,273

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Cys211Ser
Coding: c.632G>C
MANE Select: NM_001378454
dbSNP: rs770306871
Type: single nucleotide variant
Location: chr2:73419304 (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.Cys211= Likely benign ★ same residue
ALMS1 p.Cys211Ter Likely 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

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-cys211ser (accessed [today's date]).

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