Is NHS p.Ser774= (c.2322C>T) pathogenic?

NHS p.Ser774= (c.2322C>T) is classified Likely benign in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-01). Ultra-rare (popmax 0.023%, mid); Associated with Nance-Horan syndrome.

What condition is associated with NHS p.Ser774= (c.2322C>T)?

NHS p.Ser774= (c.2322C>T) is associated with Nance-Horan syndrome (ClinVar).

How common is NHS p.Ser774= (c.2322C>T) in the general population?

NHS p.Ser774= (c.2322C>T) is ultra-rare (popmax 0.023%, mid) (gnomAD).

NHS p.Ser774=

c.2322C>T · rs1043928584 · VCV3001960

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.023%, mid)

Conditions

Nance-Horan syndrome

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 2.8	GERP 1.1, phastCons 1
Overall
CADD	8.421	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.023% Middle Eastern · 1/4,354 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000413% 5/1,212,007 alleles · ultra-rare exomes 5/1,098,096 · genomes 0/113,911 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.023%	4,354
Remaining individualsnot grpmax-eligible	0.0021%	47,650
European (non-Finnish)	0.000335%	298,493

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.Ser774=
Coding: c.2322C>T
MANE Select: NM_001291867
dbSNP: rs1043928584
Type: single nucleotide variant
Location: chrX:17726428 (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-ser774 (accessed [today's date]).

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