Is UBA1 p.Pro229= (c.687C>T) pathogenic?

UBA1 p.Pro229= (c.687C>T) is classified Likely benign in UBA1 (ClinVar, Single submitter, 2 submitters; last evaluated 2018-10-16). Very rare (popmax 0.00346%, nfe); Associated with infantile-onset X-linked spinal muscular atrophy.

What condition is associated with UBA1 p.Pro229= (c.687C>T)?

UBA1 p.Pro229= (c.687C>T) is associated with infantile-onset X-linked spinal muscular atrophy (ClinVar).

How common is UBA1 p.Pro229= (c.687C>T) in the general population?

UBA1 p.Pro229= (c.687C>T) is very rare (popmax 0.00346%, nfe) (gnomAD).

How is Infantile-onset X-linked spinal muscular atrophy inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

UBA1 p.Pro229=

c.687C>T · rs782311444 · VCV746977

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00346%, nfe)

Conditions

infantile-onset X-linked spinal muscular atrophy

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 -8.6	GERP -3.7
Overall
CADD	0.046	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00346% European (non-Finnish) · 31/895,544 alleles

Filtering AF 0.00248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00216%

Overall 0.00305% 37/1,211,890 alleles · very rare exomes 37/1,098,188 · genomes 0/113,702 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00853%	11,728
Remaining individualsnot grpmax-eligible	0.0042%	23,823
European (non-Finnish)grpmax	0.00346%	28,889

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: UBA1
Protein: p.Pro229=
Coding: c.687C>T
MANE Select: NM_003334
dbSNP: rs782311444
Type: single nucleotide variant
Location: chrX:47201486 (GRCh38)
Structure: AlphaFold pLDDT 92.71 · 11 PDB
Residue 229: the '2 approximate repeats' region; a β-strand

Full UBA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

infantile-onset X-linked spinal muscular atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Infantile-onset X-linked spinal muscular atrophy (Orphanet):

Inheritance: X-linked recessive
Onset: Neonatal

Similar variants

UBA1 c.910-9C>G Uncertain significance ★★ same condition
UBA1 p.Ala136Ser Uncertain significance ★★ ⚠ same condition
UBA1 p.Ala391Thr Uncertain significance ★★ ⚠ same condition
UBA1 p.Arg288His Uncertain significance ★★ ⚠ same condition
UBA1 p.Arg345Gln Uncertain significance ★★ ⚠ same condition
UBA1 p.Arg544Trp Uncertain significance ★★ ⚠ same condition
UBA1 p.Arg693Cys Uncertain significance ★★ ⚠ same condition
UBA1 p.Arg699Gln 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/uba1-p-pro229 (accessed [today's date]).

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