Is NSF p.Pro563Arg (c.1688C>G) pathogenic?

NSF p.Pro563Arg (c.1688C>G) is classified Likely pathogenic in NSF (ClinVar, Single submitter, 2 submitters; last evaluated 2023-07-24). AlphaMissense: likely pathogenic (0.9694); No allele count reported in gnomAD v4.1 (AN 1,612,474); Associated with developmental and epileptic encephalopathy 96.

What condition is associated with NSF p.Pro563Arg (c.1688C>G)?

NSF p.Pro563Arg (c.1688C>G) is associated with developmental and epileptic encephalopathy 96 (ClinVar).

How common is NSF p.Pro563Arg (c.1688C>G) in the general population?

NSF p.Pro563Arg (c.1688C>G) is no allele count reported in gnomAD v4.1 (AN 1,612,474) (gnomAD).

What do computational predictors say about NSF p.Pro563Arg (c.1688C>G)?

AlphaMissense predicts likely pathogenic (score 0.9694) — an in-silico prediction, not a clinical call.

NSF p.Pro563Arg

c.1688C>G · rs2146266663 · VCV2434446

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9694 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,474)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

developmental and epileptic encephalopathy 96

Computational evidence

Protein change
AlphaMissense	0.9694	likely pathogenic ✓ concordant with ClinVar
REVEL	0.935	strongly pathogenic-leaning
SaProt	LLR -16.30	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.7	GERP 3.5, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 51 kb · p 4.1e-10 · regional, not allelic
Overall
CADD	25.9	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

No allele count reported in gnomAD v4.1 (AN 1,612,474). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: NSF
Protein: p.Pro563Arg
Coding: c.1688C>G
MANE Select: NM_001006607 · reported on NM_006178
dbSNP: rs2146266663
Type: single nucleotide variant
Location: chr17:46713913 (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-pro563arg (accessed [today's date]).

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