Is ALMS1 p.Phe3312Val (c.9934T>G) pathogenic?

ALMS1 p.Phe3312Val (c.9934T>G) is classified Uncertain significance in ALMS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-02). AlphaMissense: likely pathogenic (0.8327); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with ALMS1 p.Phe3312Val (c.9934T>G)?

ALMS1 p.Phe3312Val (c.9934T>G) is associated with Cardiovascular phenotype (ClinVar).

How common is ALMS1 p.Phe3312Val (c.9934T>G) in the general population?

ALMS1 p.Phe3312Val (c.9934T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ALMS1 p.Phe3312Val (c.9934T>G)?

AlphaMissense predicts likely pathogenic (score 0.8327) — an in-silico prediction, not a clinical call.

ALMS1 p.Phe3312Val

c.9934T>G · VCV4275230

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8327 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8327	likely pathogenic · top 2% in ALMS1
REVEL	0.183	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 4.8	GERP -0.58, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 224 kb · p 1.9e-16 · regional, not allelic
Overall
CADD	22.2	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

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.Phe3312Val
Coding: c.9934T>G
MANE Select: NM_001378454
Type: single nucleotide variant
Location: chr2:73550293 (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

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

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
ALMS1 p.Arg1818Ter Pathogenic/Likely pathogenic ★★ same condition
ALMS1 p.Arg2145Ter Pathogenic ★★ same condition
ALMS1 p.Arg3180Gln 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-phe3312val (accessed [today's date]).

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