Is UBQLN2 p.Pro17Ser (c.49C>T) pathogenic?

UBQLN2 p.Pro17Ser (c.49C>T) is classified Uncertain significance in UBQLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-07). AlphaMissense: likely benign (0.0677); Absent from gnomAD v4.1; Associated with amyotrophic lateral sclerosis type 15.

What condition is associated with UBQLN2 p.Pro17Ser (c.49C>T)?

UBQLN2 p.Pro17Ser (c.49C>T) is associated with amyotrophic lateral sclerosis type 15 (ClinVar).

How common is UBQLN2 p.Pro17Ser (c.49C>T) in the general population?

UBQLN2 p.Pro17Ser (c.49C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about UBQLN2 p.Pro17Ser (c.49C>T)?

AlphaMissense predicts likely benign (score 0.0677) — an in-silico prediction, not a clinical call.

UBQLN2 p.Pro17Ser

c.49C>T · rs1378794338 · VCV2169931

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0677 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

amyotrophic lateral sclerosis type 15

Computational evidence

Protein change
AlphaMissense	0.0677	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.019	phastCons 0.41
Regional constraint	o/e 1.41	unconstrained · MANE · 85 bp · p 0.03 · regional, not allelic
Overall
CADD	18.27	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 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: UBQLN2
Protein: p.Pro17Ser
Coding: c.49C>T
MANE Select: NM_013444
dbSNP: rs1378794338
Type: single nucleotide variant
Location: chrX:56563922 (GRCh38)
Structure: AlphaFold pLDDT 62.24 · 4 PDB
Residue 17: the 'disordered' region

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.Pro17= Benign ★ same residue
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

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-pro17ser (accessed [today's date]).

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