Is UBASH3A p.Ser95= (c.285C>T) pathogenic?

UBASH3A p.Ser95= (c.285C>T) is classified Likely benign in UBASH3A (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-04). Ultra-rare (popmax 0.028%, afr); Associated with UBASH3A-related disorder.

What condition is associated with UBASH3A p.Ser95= (c.285C>T)?

UBASH3A p.Ser95= (c.285C>T) is associated with UBASH3A-related disorder (ClinVar).

How common is UBASH3A p.Ser95= (c.285C>T) in the general population?

UBASH3A p.Ser95= (c.285C>T) is ultra-rare (popmax 0.028%, afr) (gnomAD).

UBASH3A p.Ser95=

c.285C>T · rs139067853 · VCV3030883

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.028%, afr)

Conditions

UBASH3A-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 0.65, phastCons 0.99
Overall
CADD	13.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.028% African / African-American · 21/74,904 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0157%

Overall 0.00186% 30/1,614,022 alleles · ultra-rare exomes 13/1,461,866 · genomes 17/152,156 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.028%	3,567
Admixed American	0.015%	6,666

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: UBASH3A
Protein: p.Ser95=
Coding: c.285C>T
MANE Select: NM_018961
dbSNP: rs139067853
Type: single nucleotide variant
Location: chr21:42409539 (GRCh38)
Gene constraint: LOEUF 1.038 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.62 · 2 PDB

Full UBASH3A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UBASH3A-related disorder

Similar variants

UBASH3A p.Ser95Ile Uncertain significance ★ ⚠ same residue
UBASH3A p.Ile463Phe Uncertain significance ★★ ⚠ same type
CLIP4 p.Thr555= Benign ★★ same type
UBASH3A c.1393+3A>C Benign ★★ same type
UBASH3A p.Gly601= Benign ★★ same type
UBASH3A p.Ile303= Benign ★★ same type
UBASH3A p.Ile658Val Benign ★★ same type
UBASH3A p.Phe304= Benign ★★ same type

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/ubash3a-p-ser95 (accessed [today's date]).

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