Is NHS p.Val358= (c.1074G>A) pathogenic?

NHS p.Val358= (c.1074G>A) is classified Uncertain significance in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-10). Absent from gnomAD v4.1; Associated with Nance-Horan syndrome.

What condition is associated with NHS p.Val358= (c.1074G>A)?

NHS p.Val358= (c.1074G>A) is associated with Nance-Horan syndrome (ClinVar).

How common is NHS p.Val358= (c.1074G>A) in the general population?

NHS p.Val358= (c.1074G>A) is absent from gnomAD v4.1 (gnomAD).

NHS p.Val358=

c.1074G>A · rs2066406785 · VCV1086277

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/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.56	donor gain · deltas
Pangolin	Δ0.70	gain · loss 0.52 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.6	GERP 0.05, phastCons 1
Overall
CADD	17.44	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.Val358=
Coding: c.1074G>A
MANE Select: NM_001291867
dbSNP: rs2066406785
Type: single nucleotide variant
Location: chrX:17721599 (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-val358 (accessed [today's date]).

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