Is NUS1 p.Arg20Pro (c.59G>C) pathogenic?

NUS1 p.Arg20Pro (c.59G>C) is classified Uncertain significance in NUS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: ambiguous (0.56); Absent from gnomAD v4.1; Associated with congenital disorder of glycosylation, type Iaa.

What condition is associated with NUS1 p.Arg20Pro (c.59G>C)?

NUS1 p.Arg20Pro (c.59G>C) is associated with congenital disorder of glycosylation, type Iaa (ClinVar).

How common is NUS1 p.Arg20Pro (c.59G>C) in the general population?

NUS1 p.Arg20Pro (c.59G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NUS1 p.Arg20Pro (c.59G>C)?

AlphaMissense predicts ambiguous (score 0.56) — an in-silico prediction, not a clinical call.

NUS1 p.Arg20Pro

c.59G>C · rs529145043 · VCV2820331

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.56 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

congenital disorder of glycosylation, type Iaa

Computational evidence

Protein change
AlphaMissense	0.56	ambiguous
REVEL	0.199	benign-leaning
SaProt	LLR -11.26	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP 2.7, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 18 kb · p 0.003 · regional, not allelic
Overall
CADD	25.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NUS1
Protein: p.Arg20Pro
Coding: c.59G>C
MANE Select: NM_138459
dbSNP: rs529145043
Type: single nucleotide variant
Location: chr6:117675729 (GRCh38)
Gene constraint: LOEUF 0.182 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 82.01 · 9 PDB

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.Arg20Gly Uncertain significance ★ ⚠ same residue
NUS1 p.Arg20Cys Uncertain significance ★ ⚠ same residue
NUS1 c.415+1G>A Pathogenic/Likely pathogenic ★★ same condition
NUS1 c.692-2A>G Likely pathogenic ★★ same condition
NUS1 p.Arg290Cys Pathogenic/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

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-arg20pro (accessed [today's date]).

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