Is UBQLN2 p.Phe46= (c.138C>T) pathogenic?

UBQLN2 p.Phe46= (c.138C>T) is classified Likely benign in UBQLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-23). Absent from gnomAD v4.1; Associated with amyotrophic lateral sclerosis type 15.

What condition is associated with UBQLN2 p.Phe46= (c.138C>T)?

UBQLN2 p.Phe46= (c.138C>T) is associated with amyotrophic lateral sclerosis type 15 (ClinVar).

How common is UBQLN2 p.Phe46= (c.138C>T) in the general population?

UBQLN2 p.Phe46= (c.138C>T) is absent from gnomAD v4.1 (gnomAD).

UBQLN2 p.Phe46=

c.138C>T · rs2519961608 · VCV1910274

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

amyotrophic lateral sclerosis type 15

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 1.4	phastCons 1
Overall
CADD	12.82	PHRED · no single calibrated threshold — expert panels disagree

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: UBQLN2
Protein: p.Phe46=
Coding: c.138C>T
MANE Select: NM_013444
dbSNP: rs2519961608
Type: single nucleotide variant
Location: chrX:56564011 (GRCh38)
Structure: AlphaFold pLDDT 62.24 · 4 PDB
Residue 46: the ubiquitin-like domain; a β-strand

Full UBQLN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

amyotrophic lateral sclerosis type 15 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UBQLN2 p.Pro497His Pathogenic ★★ same condition
UBQLN2 p.Ala26Ser Uncertain significance ★★ ⚠ same condition
UBQLN2 p.Ala282Thr Uncertain significance ★★ ⚠ same condition
UBQLN2 p.Ala361Thr Uncertain significance ★★ ⚠ same condition
UBQLN2 p.Ala523Val Uncertain significance ★★ ⚠ same condition
UBQLN2 p.Arg270Cys Uncertain significance ★★ ⚠ same condition
UBQLN2 p.Asn122Asp Uncertain significance ★★ ⚠ same condition
UBQLN2 p.Asp85His 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/ubqln2-p-phe46 (accessed [today's date]).

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