Is ALMS1 p.Ser1236Phe (c.3707C>T) pathogenic?

ALMS1 p.Ser1236Phe (c.3707C>T) is classified Uncertain significance in ALMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-06). AlphaMissense: likely benign (0.2406); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Ser1236Phe (c.3707C>T)?

ALMS1 p.Ser1236Phe (c.3707C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is ALMS1 p.Ser1236Phe (c.3707C>T) in the general population?

ALMS1 p.Ser1236Phe (c.3707C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALMS1 p.Ser1236Phe (c.3707C>T)?

AlphaMissense predicts likely benign (score 0.2406) — an in-silico prediction, not a clinical call.

ALMS1 p.Ser1236Phe

c.3707C>T · rs2466099128 · VCV1734197

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2406 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.2406	likely benign
REVEL	0.127	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.13	GERP 1.3
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	15.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ALMS1
Protein: p.Ser1236Phe
Coding: c.3707C>T
MANE Select: NM_001378454
dbSNP: rs2466099128
Type: single nucleotide variant
Location: chr2:73450234 (GRCh38)
Gene constraint: LOEUF 0.825 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 1236: the '34 x 47 aa approximate tandem repeat' region; the 'disordered' 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

Similar variants

ALMS1 p.Ser1236Pro Uncertain significance ★ ⚠ same residue
ALMS1 p.Ser1236Thr Uncertain significance ★ ⚠ same residue
ALMS1 p.Ser1236Ala Uncertain significance ⚠ same residue
ALMS1 c.10214-2A>G Likely pathogenic ★★ same condition
ALMS1 c.12114+1G>A Likely pathogenic ★★ same condition
ALMS1 c.12299-2A>G Pathogenic/Likely pathogenic ★★ same condition
ALMS1 c.1432+1G>T Likely pathogenic ★★ same condition
ALMS1 c.451-2A>G 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-ser1236phe (accessed [today's date]).

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