Is NUS1 p.Arg290= (c.870T>G) pathogenic?

NUS1 p.Arg290= (c.870T>G) is classified Likely benign in NUS1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-22). Very rare (popmax 0.0045%, nfe); Associated with congenital disorder of glycosylation, type Iaa.

What condition is associated with NUS1 p.Arg290= (c.870T>G)?

NUS1 p.Arg290= (c.870T>G) is associated with congenital disorder of glycosylation, type Iaa (ClinVar).

How common is NUS1 p.Arg290= (c.870T>G) in the general population?

NUS1 p.Arg290= (c.870T>G) is very rare (popmax 0.0045%, nfe) (gnomAD).

NUS1 p.Arg290=

c.870T>G · rs529109392 · VCV1627808

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0045%, nfe)

Conditions

congenital disorder of glycosylation, type Iaa

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 0.17	GERP -0.94, phastCons 0.12
Overall
CADD	7.491	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0045% European (non-Finnish) · 53/1,178,676 alleles

Filtering AF 0.00351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00341% 55/1,612,248 alleles · very rare exomes 48/1,460,106 · genomes 7/152,142 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0045%	22,239
Remaining individualsnot grpmax-eligible	0.0016%	62,388
African / African-American	0.00134%	74,834

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: NUS1
Protein: p.Arg290=
Coding: c.870T>G
MANE Select: NM_138459
dbSNP: rs529109392
Type: single nucleotide variant
Location: chr6:117707003 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.01 · 9 PDB
Residue 290: a UniProt-annotated variant site (found in a patient with progressive myoclonus epilepsy; likely pathogenic); a UniProt-annotated variant site (in cdg1aa; loss of function in protein glycosylation; 5-fold reduction in catalytic activity and reduced affinity for fpp and ipp)

Full NUS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital disorder of glycosylation, type Iaa — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NUS1 p.Arg290Cys Pathogenic/Likely pathogenic ★★ same residue
NUS1 p.Arg290His Conflicting classifications of pathogenicity ★ ⚠ same residue
NUS1 c.415+1G>A Pathogenic/Likely pathogenic ★★ same condition
NUS1 c.692-2A>G Likely pathogenic ★★ same condition
NUS1 p.Leu240Ter Pathogenic/Likely pathogenic ★★ same condition
NUS1 p.Ala44Thr Uncertain significance ★★ ⚠ same condition
NUS1 p.Ala79Val Uncertain significance ★★ ⚠ same condition
NUS1 p.Arg10Trp 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/nus1-p-arg290 (accessed [today's date]).

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