Is UBA1 p.Asp705= (c.2115C>T) pathogenic?

UBA1 p.Asp705= (c.2115C>T) is classified Likely benign in UBA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). Ultra-rare (popmax 0.0178%, eas); Associated with infantile-onset X-linked spinal muscular atrophy.

What condition is associated with UBA1 p.Asp705= (c.2115C>T)?

UBA1 p.Asp705= (c.2115C>T) is associated with infantile-onset X-linked spinal muscular atrophy (ClinVar).

How common is UBA1 p.Asp705= (c.2115C>T) in the general population?

UBA1 p.Asp705= (c.2115C>T) is ultra-rare (popmax 0.0178%, eas) (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.Asp705=

c.2115C>T · rs1481710267 · VCV1660434

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

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 0.42	GERP -0.43, phastCons 0.99
Overall
CADD	9.911	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% East Asian · 6/33,794 alleles

Filtering AF 0.00765% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00527%

Overall 0.000578% 7/1,210,819 alleles · ultra-rare exomes 5/1,098,234 · genomes 2/112,585 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,632
Remaining individualsnot grpmax-eligible	0.0021%	47,613

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.Asp705=
Coding: c.2115C>T
MANE Select: NM_003334
dbSNP: rs1481710267
Type: single nucleotide variant
Location: chrX:47210039 (GRCh38)
Structure: AlphaFold pLDDT 92.71 · 11 PDB
Residue 705: an α-helix

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-asp705 (accessed [today's date]).

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