Is NHS p.Arg900Ter (c.2698C>T) pathogenic?

NHS p.Arg900Ter (c.2698C>T) is classified Pathogenic in NHS (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-09). Very rare (popmax 8.25e-05%); Associated with Nance-Horan syndrome.

What condition is associated with NHS p.Arg900Ter (c.2698C>T)?

NHS p.Arg900Ter (c.2698C>T) is associated with Nance-Horan syndrome (ClinVar).

How common is NHS p.Arg900Ter (c.2698C>T) in the general population?

NHS p.Arg900Ter (c.2698C>T) is very rare (popmax 8.25e-05%) (gnomAD).

NHS p.Arg900Ter

c.2698C>T · VCV4687062

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.25e-05%)

Conditions

Nance-Horan syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 2, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.25e-05%

Overall 8.25e-05% 1/1,211,671 alleles · very rare exomes 1/1,098,187 · genomes 0/113,484 · 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.Arg900Ter
Coding: c.2698C>T
MANE Select: NM_001291867
Type: single nucleotide variant
Location: chrX:17726804 (GRCh38)
Structure: AlphaFold pLDDT 43.65

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

Disease context

Nance-Horan syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NHS p.Arg248Ter Pathogenic ★★ same condition
NHS p.Arg394Ter Pathogenic ★★ same condition
NHS p.Gln411Ter Pathogenic ★★ same condition
NHS p.Gln80Ter Pathogenic/Likely pathogenic ★★ same condition
NHS p.Ala564Val Uncertain significance ★★ same condition
NHS p.Ala745Val Uncertain significance ★★ same condition
NHS p.Arg162Cys Uncertain significance ★★ same condition
NHS p.Arg176Gly 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/nhs-p-arg900ter (accessed [today's date]).

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