Is NDST1 p.Pro309= (c.927A>G) pathogenic?

NDST1 p.Pro309= (c.927A>G) is classified Benign/Likely benign in NDST1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-16). Low-frequency (popmax 4.38%, sas); Associated with intellectual disability, autosomal recessive 46.

What condition is associated with NDST1 p.Pro309= (c.927A>G)?

NDST1 p.Pro309= (c.927A>G) is associated with intellectual disability, autosomal recessive 46 (ClinVar).

How common is NDST1 p.Pro309= (c.927A>G) in the general population?

NDST1 p.Pro309= (c.927A>G) is low-frequency (popmax 4.38%, sas) (gnomAD).

NDST1 p.Pro309=

c.927A>G · rs137903526 · VCV717699

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.38%, sas)

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 -1.5	GERP -5.6
Overall
CADD	1.927	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.38% South Asian · 3,990/91,054 alleles

Filtering AF 4.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.22%

Overall 0.432% 6,975/1,614,080 alleles · low-frequency exomes 6,540/1,461,780 · genomes 435/152,300 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	4.38%	23
Middle Eastern	0.759%	132
Remaining individualsnot grpmax-eligible	0.44%	227
European (non-Finnish)	0.204%	490
Admixed American	0.173%	577
Ashkenazi Jewishnot grpmax-eligible	0.155%	644
Finnishnot grpmax-eligible	0.089%	1,123
African / African-American	0.0573%	1,746
East Asian	0.0134%	7,478

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.Pro309=
Coding: c.927A>G
MANE Select: NM_001543
dbSNP: rs137903526
Type: single nucleotide variant
Location: chr5:150528217 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 90.55 · 5 PDB
Residue 309: 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-pro309 (accessed [today's date]).

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