Is UBA7 p.Arg839Pro (c.2516G>C) pathogenic?

UBA7 p.Arg839Pro (c.2516G>C) is classified Benign in UBA7 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-20). AlphaMissense: likely benign (0.1988); Rare (popmax 0.934%, eas); Associated with UBA7-related disorder.

What condition is associated with UBA7 p.Arg839Pro (c.2516G>C)?

UBA7 p.Arg839Pro (c.2516G>C) is associated with UBA7-related disorder (ClinVar).

How common is UBA7 p.Arg839Pro (c.2516G>C) in the general population?

UBA7 p.Arg839Pro (c.2516G>C) is rare (popmax 0.934%, eas) (gnomAD).

What do computational predictors say about UBA7 p.Arg839Pro (c.2516G>C)?

AlphaMissense predicts likely benign (score 0.1988) — an in-silico prediction, not a clinical call.

UBA7 p.Arg839Pro

c.2516G>C · rs118020287 · VCV3051003

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1988 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.934%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

UBA7-related disorder

Computational evidence

Protein change
AlphaMissense	0.1988	likely benign
REVEL	0.219	benign-leaning
SaProt	LLR -10.05	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,757 bp · p 0.2 · regional, not allelic
Overall
CADD	15.32	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 0.934% East Asian · 419/44,884 alleles

Filtering AF 0.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.831%

Overall 0.0274% 443/1,614,112 alleles · rare exomes 361/1,461,748 · genomes 82/152,364 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.934%	107
Remaining individualsnot grpmax-eligible	0.0288%	3,472
Admixed American	0.00667%	15,002
African / African-American	0.00133%	75,064
South Asian	0.0011%	91,076

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: UBA7
Protein: p.Arg839Pro
Coding: c.2516G>C
MANE Select: NM_003335
dbSNP: rs118020287
Type: single nucleotide variant
Location: chr3:49808027 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 6 PDB
Residue 839: an α-helix; a UniProt-annotated variant site (found in a small consanguineous family with learning disability; uncertain significance)

Full UBA7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

UBA7-related disorder

Similar variants

UBA7 p.Arg839Cys Uncertain significance ★ ⚠ same residue
UBA7 p.Arg839His Uncertain significance ★ ⚠ same residue
UBA7 p.Gln433Ter Uncertain significance ★ same condition
UBA7 c.2910-9C>T Likely benign same condition
UBA7 p.Ala391= Likely benign same condition
UBA7 p.Ala88= Benign same condition
UBA7 p.Arg414His Likely benign ⚠ same condition
UBA7 p.Leu512= Likely benign 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/uba7-p-arg839pro (accessed [today's date]).

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