Is ALMS1 p.Ser1065Pro (c.3193T>C) pathogenic?

ALMS1 p.Ser1065Pro (c.3193T>C) is classified Benign/Likely benign in ALMS1 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0541); Low-frequency (popmax 1.79%, afr); Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Ser1065Pro (c.3193T>C)?

ALMS1 p.Ser1065Pro (c.3193T>C) is associated with Cardiovascular phenotype, Alstrom syndrome, monogenic diabetes (ClinVar).

How common is ALMS1 p.Ser1065Pro (c.3193T>C) in the general population?

ALMS1 p.Ser1065Pro (c.3193T>C) is low-frequency (popmax 1.79%, afr) (gnomAD).

What do computational predictors say about ALMS1 p.Ser1065Pro (c.3193T>C)?

AlphaMissense predicts likely benign (score 0.0541) — an in-silico prediction, not a clinical call.

ALMS1 p.Ser1065Pro

c.3193T>C · rs28730852 · VCV387347

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.0541 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.79%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.0541	likely benign
REVEL	0.018	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 -20	GERP -3
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	0.011	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 1.79% African / African-American · 1,343/75,012 alleles

Filtering AF 1.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.68%

Overall 0.098% 1,582/1,614,016 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.79%	56
Admixed American	0.178%	561
Remaining individualsnot grpmax-eligible	0.154%	651
Middle Eastern	0.0495%	2,021
European (non-Finnish)	0.0028%	35,756

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.Ser1065Pro
Coding: c.3193T>C
MANE Select: NM_001378454
dbSNP: rs28730852
Type: single nucleotide variant
Location: chr2:73449720 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1065: 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 monogenic diabetes

Similar variants

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
ALMS1 c.11669-1G>C 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-ser1065pro (accessed [today's date]).

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