Is NHS p.Phe282Val (c.844T>G) pathogenic?

NHS p.Phe282Val (c.844T>G) is classified Uncertain significance in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-23). Absent from gnomAD v4.1; Associated with Nance-Horan syndrome.

What condition is associated with NHS p.Phe282Val (c.844T>G)?

NHS p.Phe282Val (c.844T>G) is associated with Nance-Horan syndrome (ClinVar).

How common is NHS p.Phe282Val (c.844T>G) in the general population?

NHS p.Phe282Val (c.844T>G) is absent from gnomAD v4.1 (gnomAD).

NHS p.Phe282Val

c.844T>G · rs2519884491 · VCV2876334

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Nance-Horan syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.127	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 357 kb · p 1.3e-14 · regional, not allelic
Overall
CADD	17.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: NHS
Protein: p.Phe282Val
Coding: c.844T>G
MANE Select: NM_001291867
dbSNP: rs2519884491
Type: single nucleotide variant
Location: chrX:17692460 (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.Arg900Ter 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

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-phe282val (accessed [today's date]).

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