Is ALMS1 p.Phe730= (c.2190C>T) pathogenic?

ALMS1 p.Phe730= (c.2190C>T) is classified Benign/Likely benign in ALMS1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-02-04). Common (popmax 75%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Phe730= (c.2190C>T)?

ALMS1 p.Phe730= (c.2190C>T) is associated with Cardiovascular phenotype, Alstrom syndrome (ClinVar).

ALMS1 p.Phe730=

Q: How common is ALMS1 p.Phe730= (c.2190C>T) in the general population?

ALMS1 p.Phe730= (c.2190C>T) is common (popmax 75%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2190C>T · rs7598901 · VCV383768

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

gnomAD v4.1

Common

common (popmax 75%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

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 -4.6	GERP -2.8
Overall
CADD	2.372	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 75% East Asian · 33,615/44,842 alleles

Filtering AF 74.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 74%

Overall 60.9% 982,511/1,613,450 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	75%	1
Amishnot grpmax-eligible	69%	1
South Asian	66.2%	2
European (non-Finnish)	62.8%	2
Ashkenazi Jewishnot grpmax-eligible	62.7%	2
Remaining individualsnot grpmax-eligible	61.7%	2
Finnishnot grpmax-eligible	61.4%	2
Middle Eastern	61.3%	2
Admixed American	54.7%	2
African / African-American	18.8%	5

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.Phe730=
Coding: c.2190C>T
MANE Select: NM_001378454
dbSNP: rs7598901
Type: single nucleotide variant
Location: chr2:73448717 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 730: 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.Phe730Leu 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
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-phe730 (accessed [today's date]).

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