Is UBQLN2 p.Pro17= (c.51T>A) pathogenic?

UBQLN2 p.Pro17= (c.51T>A) is classified Benign in UBQLN2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-26). Rare (popmax 0.244%, eas); Associated with amyotrophic lateral sclerosis type 15.

What condition is associated with UBQLN2 p.Pro17= (c.51T>A)?

UBQLN2 p.Pro17= (c.51T>A) is associated with amyotrophic lateral sclerosis type 15 (ClinVar).

How common is UBQLN2 p.Pro17= (c.51T>A) in the general population?

UBQLN2 p.Pro17= (c.51T>A) is rare (popmax 0.244%, eas) (gnomAD).

UBQLN2 p.Pro17=

c.51T>A · rs371163085 · VCV1664641

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.244%, eas)

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 -0.83	phastCons 0.004
Overall
CADD	12.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.244% East Asian · 77/31,539 alleles

Filtering AF 0.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.00692% 80/1,156,539 alleles · rare exomes 67/1,043,778 · genomes 13/112,761 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.244%	410
Remaining individualsnot grpmax-eligible	0.00662%	15,104

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: UBQLN2
Protein: p.Pro17=
Coding: c.51T>A
MANE Select: NM_013444
dbSNP: rs371163085
Type: single nucleotide variant
Location: chrX:56563924 (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.Pro17Ser Uncertain significance ★ ⚠ 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-pro17 (accessed [today's date]).

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