Is UPB1 p.Ala366Val (c.1097C>T) pathogenic?

UPB1 p.Ala366Val (c.1097C>T) is classified Uncertain significance in UPB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-21). AlphaMissense: likely benign (0.1923); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with UPB1 p.Ala366Val (c.1097C>T)?

UPB1 p.Ala366Val (c.1097C>T) is associated with Inborn genetic diseases (ClinVar).

How common is UPB1 p.Ala366Val (c.1097C>T) in the general population?

UPB1 p.Ala366Val (c.1097C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UPB1 p.Ala366Val (c.1097C>T)?

AlphaMissense predicts likely benign (score 0.1923) — an in-silico prediction, not a clinical call.

UPB1 p.Ala366Val

c.1097C>T · rs2517988982 · VCV2338718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1923 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1923	likely benign
REVEL	0.597	indeterminate
SaProt	LLR -10.81	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.61, phastCons 0.97
Regional constraint	o/e 0.99	unconstrained · MANE · 30 kb · p 0.76 · regional, not allelic
Overall
CADD	21.2	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: UPB1
Protein: p.Ala366Val
Coding: c.1097C>T
MANE Select: NM_016327
dbSNP: rs2517988982
Type: single nucleotide variant
Location: chr22:24525736 (GRCh38)
Gene constraint: LOEUF 0.982 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 97.10 · 2 PDB
Residue 366: an α-helix

Full UPB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UPB1 p.Ala4Thr Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg236Gln Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg288Gln Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg332Cys Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg332His Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg334Trp Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg68Gln Uncertain significance ★★ ⚠ same condition
UPB1 p.Arg70Cys Uncertain significance ★★ ⚠ 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/upb1-p-ala366val (accessed [today's date]).

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