Is NUS1 p.Pro51= (c.153G>T) pathogenic?

NUS1 p.Pro51= (c.153G>T) is classified Likely benign in NUS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-18). Ultra-rare (popmax 0.0913%, mid); Associated with congenital disorder of glycosylation, type Iaa.

What condition is associated with NUS1 p.Pro51= (c.153G>T)?

NUS1 p.Pro51= (c.153G>T) is associated with congenital disorder of glycosylation, type Iaa (ClinVar).

How common is NUS1 p.Pro51= (c.153G>T) in the general population?

NUS1 p.Pro51= (c.153G>T) is ultra-rare (popmax 0.0913%, mid) (gnomAD).

NUS1 p.Pro51=

c.153G>T · rs868271796 · VCV1575887

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0913%, mid)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.6	GERP 0.24, phastCons 1
Overall
CADD	13.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0913% Middle Eastern · 4/4,382 alleles

Filtering AF 0.0311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00271% 42/1,551,284 alleles · ultra-rare exomes 39/1,399,190 · genomes 3/152,094 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0913%	1,096
Admixed American	0.00775%	12,897
Remaining individualsnot grpmax-eligible	0.005%	20,002
European (non-Finnish)	0.0027%	37,081

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.Pro51=
Coding: c.153G>T
MANE Select: NM_138459
dbSNP: rs868271796
Type: single nucleotide variant
Location: chr6:117675823 (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.Pro51Leu 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
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-pro51 (accessed [today's date]).

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