Is NDST1 p.Pro250= (c.750A>G) pathogenic?

NDST1 p.Pro250= (c.750A>G) is classified Benign in NDST1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-03). Common (popmax 52.9%, amr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, autosomal recessive 46.

What condition is associated with NDST1 p.Pro250= (c.750A>G)?

NDST1 p.Pro250= (c.750A>G) is associated with intellectual disability, autosomal recessive 46 (ClinVar).

NDST1 p.Pro250=

Q: How common is NDST1 p.Pro250= (c.750A>G) in the general population?

NDST1 p.Pro250= (c.750A>G) is common (popmax 52.9%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.750A>G · rs2273234 · VCV1302757

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 52.9%, amr) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, autosomal recessive 46

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 -6.2	GERP -5.7
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 52.9% Admixed American · 31,607/59,776 alleles

Filtering AF 52.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 52.2%

Overall 43.9% 707,141/1,612,592 alleles · common exomes 650,770/1,460,448 · genomes 56,371/152,144 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	52.9%	2
Finnishnot grpmax-eligible	51.3%	2
European (non-Finnish)	46.5%	2
Amishnot grpmax-eligible	45.7%	2
South Asian	42.4%	2
Remaining individualsnot grpmax-eligible	41.1%	2
Ashkenazi Jewishnot grpmax-eligible	32%	3
Middle Eastern	30.1%	3
African / African-American	15.8%	6
East Asian	14%	7

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: NDST1
Protein: p.Pro250=
Coding: c.750A>G
MANE Select: NM_001543
dbSNP: rs2273234
Type: single nucleotide variant
Location: chr5:150528040 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 90.55 · 5 PDB
Residue 250: the 'heparan sulfate n-deacetylase 1' region

Full NDST1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual disability, autosomal recessive 46 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NDST1 p.Gly611Ser Pathogenic/Likely pathogenic ★★ same condition
NDST1 p.Arg112Cys Uncertain significance ★★ ⚠ same condition
NDST1 p.Arg130Cys Uncertain significance ★★ ⚠ same condition
NDST1 p.Arg244Cys Uncertain significance ★★ ⚠ same condition
NDST1 p.Arg454Cys Uncertain significance ★★ ⚠ same condition
NDST1 p.Arg688Gln Uncertain significance ★★ ⚠ same condition
NDST1 p.Arg875Ter Uncertain significance ★★ same condition
NDST1 p.His13Gln 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/ndst1-p-pro250 (accessed [today's date]).

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