Is UBA6 p.Cys17Ser (c.50G>C) pathogenic?

UBA6 p.Cys17Ser (c.50G>C) is classified Uncertain significance in UBA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-18). AlphaMissense: likely benign (0.0766); Rare (popmax 0.125%, sas).

How common is UBA6 p.Cys17Ser (c.50G>C) in the general population?

UBA6 p.Cys17Ser (c.50G>C) is rare (popmax 0.125%, sas) (gnomAD).

What do computational predictors say about UBA6 p.Cys17Ser (c.50G>C)?

AlphaMissense predicts likely benign (score 0.0766) — an in-silico prediction, not a clinical call.

UBA6 p.Cys17Ser

c.50G>C · rs534250437 · VCV2548498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0766 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.125%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0766	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -4.54	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 6.8	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 82 kb · p 0.12 · regional, not allelic
Overall
CADD	23.3	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

Grpmax group 0.125% South Asian · 114/91,080 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0994%

Overall 0.00756% 122/1,613,830 alleles · rare exomes 112/1,461,490 · genomes 10/152,340 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.125%	799
Remaining individualsnot grpmax-eligible	0.0096%	10,414
African / African-American	0.00133%	75,050
European (non-Finnish)	8.48e-05%	1,179,784

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: UBA6
Protein: p.Cys17Ser
Coding: c.50G>C
MANE Select: NM_018227
dbSNP: rs534250437
Type: single nucleotide variant
Location: chr4:67701070 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.67 · 20 PDB
Residue 17: the 'disordered' region

Full UBA6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

UBA6 p.Ala526Val Uncertain significance ★ ⚠ same type
UBA6 p.Ala540Val Uncertain significance ★ ⚠ same type
UBA6 p.Ala55Gly Uncertain significance ★ same type
UBA6 p.Ala567Val Uncertain significance ★ ⚠ same type
UBA6 p.Ala824Val Uncertain significance ★ ⚠ same type
UBA6 p.Arg248Gln Uncertain significance ★ ⚠ same type
UBA6 p.Arg513Cys Uncertain significance ★ same type
UBA6 p.Arg513His Uncertain significance ★ ⚠ 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/uba6-p-cys17ser (accessed [today's date]).

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