Is NSF p.Val602Ala (c.1805T>C) pathogenic?

NSF p.Val602Ala (c.1805T>C) is classified Likely benign in NSF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-03-23). AlphaMissense: likely pathogenic (0.9474); Absent from gnomAD v4.1; Associated with developmental and epileptic encephalopathy 96.

What condition is associated with NSF p.Val602Ala (c.1805T>C)?

NSF p.Val602Ala (c.1805T>C) is associated with developmental and epileptic encephalopathy 96 (ClinVar).

How common is NSF p.Val602Ala (c.1805T>C) in the general population?

NSF p.Val602Ala (c.1805T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NSF p.Val602Ala (c.1805T>C)?

AlphaMissense predicts likely pathogenic (score 0.9474) — an in-silico prediction, not a clinical call.

NSF p.Val602Ala

c.1805T>C · VCV4819939

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9474 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy 96

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.9474	likely pathogenic
REVEL	0.908	moderately pathogenic-leaning
SaProt	LLR -7.88	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.9	GERP 3.7, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 51 kb · p 4.1e-10 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: NSF
Protein: p.Val602Ala
Coding: c.1805T>C
MANE Select: NM_006178
Type: single nucleotide variant
Location: chr17:46726592 (GRCh38)

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

Disease context

developmental and epileptic encephalopathy 96 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/nsf-p-val602ala (accessed [today's date]).

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