Is NHS p.Ser500= (c.1500C>T) pathogenic?

NHS p.Ser500= (c.1500C>T) is classified Likely benign in NHS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-01-05). Very rare (popmax 0.00701%, afr); Associated with NHS-related disorder.

What condition is associated with NHS p.Ser500= (c.1500C>T)?

NHS p.Ser500= (c.1500C>T) is associated with NHS-related disorder (ClinVar).

How common is NHS p.Ser500= (c.1500C>T) in the general population?

NHS p.Ser500= (c.1500C>T) is very rare (popmax 0.00701%, afr) (gnomAD).

NHS p.Ser500=

c.1500C>T · rs371021798 · VCV3050218

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00701%, afr)

Conditions

NHS-related disorder

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 4.1	GERP 0.93, phastCons 1
Overall
CADD	9.529	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00701% African / African-American · 4/57,025 alleles

Filtering AF 0.00234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0014%

Overall 0.000331% 4/1,209,712 alleles · very rare exomes 0/1,098,222 · genomes 4/111,490 · joint denominator

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: NHS
Protein: p.Ser500=
Coding: c.1500C>T
MANE Select: NM_001291867
dbSNP: rs371021798
Type: single nucleotide variant
Location: chrX:17725606 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 500: the 'disordered' region

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

Disease context

NHS-related disorder

Similar variants

NHS p.Arg248Ter Pathogenic ★★ same condition
NHS p.Gln411Ter Pathogenic ★★ same condition
NHS p.Arg43Gly Uncertain significance ★★ same condition
NHS p.Gln1064Ter Likely pathogenic ★ same condition
NHS p.Glu186Ter Pathogenic ★ same condition
NHS p.Ser1327Ter Likely pathogenic ★ same condition
NHS p.Trp207Ter Likely pathogenic ★ same condition
NHS p.Asn1266Lys Conflicting classifications of pathogenicity ★ 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/nhs-p-ser500 (accessed [today's date]).

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