Is UBA6 p.Pro797Ser (c.2389C>T) pathogenic?

UBA6 p.Pro797Ser (c.2389C>T) is classified Uncertain significance in UBA6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: ambiguous (0.4084); Very rare (popmax 0.0022%, sas).

How common is UBA6 p.Pro797Ser (c.2389C>T) in the general population?

UBA6 p.Pro797Ser (c.2389C>T) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about UBA6 p.Pro797Ser (c.2389C>T)?

AlphaMissense predicts ambiguous (score 0.4084) — an in-silico prediction, not a clinical call.

UBA6 p.Pro797Ser

c.2389C>T · rs749283216 · VCV2491856

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4084 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
AlphaMissense	0.4084	ambiguous
REVEL	0.321	indeterminate
SaProt	LLR -10.40	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 82 kb · p 0.12 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/90,954 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000249% 4/1,607,624 alleles · very rare exomes 4/1,455,618 · genomes 0/152,006 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,477
European (non-Finnish)	0.00017%	587,441

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.Pro797Ser
Coding: c.2389C>T
MANE Select: NM_018227
dbSNP: rs749283216
Type: single nucleotide variant
Location: chr4:67629082 (GRCh38)
Gene constraint: LOEUF 0.868 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.67 · 20 PDB
Residue 797: an α-helix

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-pro797ser (accessed [today's date]).

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