Is NHS p.Ser643fs (c.1928del) pathogenic?

NHS p.Ser643fs (c.1928del) is classified Likely pathogenic in NHS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-23). Associated with cataract 40.

What condition is associated with NHS p.Ser643fs (c.1928del)?

NHS p.Ser643fs (c.1928del) is associated with cataract 40 (ClinVar).

How is Early onset non-syndromic cataract inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

NHS p.Ser643fs

c.1928del · VCV3775474

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

cataract 40

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 7 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1

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

Variant & gene context

Gene: NHS
Protein: p.Ser643fs
Coding: c.1928del
MANE Select: NM_001291867
Type: Deletion
Location: chrX:17726034 (GRCh38)
Structure: AlphaFold pLDDT 43.65
Residue 643: the 'disordered' region

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

Disease context

cataract 40 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

NHS p.Arg468fs Likely pathogenic ★ same condition
NHS p.Ser643Leu Conflicting classifications of pathogenicity ★ same residue
NHS p.Ser643= Benign ★ same residue
NHS p.Arg394Ter Pathogenic ★★ same condition
NHS p.Arg59Gln Uncertain significance ★★ same condition
NHS p.Asp182Glu Uncertain significance ★★ same condition
NHS p.Thr1595Pro Uncertain significance ★★ same condition
NHS c.566-10dup Benign/Likely benign ★★ 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-ser643fs (accessed [today's date]).

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