Is REST p.Pro303fs (c.908del) pathogenic?

REST p.Pro303fs (c.908del) is classified Likely pathogenic in REST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-14). No allele count reported in gnomAD v4.1 (AN 1,600,166); Associated with REST-related disorder.

What condition is associated with REST p.Pro303fs (c.908del)?

REST p.Pro303fs (c.908del) is associated with REST-related disorder (ClinVar).

How common is REST p.Pro303fs (c.908del) in the general population?

REST p.Pro303fs (c.908del) is no allele count reported in gnomAD v4.1 (AN 1,600,166) (gnomAD).

REST p.Pro303fs

c.908del · rs2475825927 · VCV2635523

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,166)

Conditions

REST-related disorder

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 2.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,166). 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: REST
Protein: p.Pro303fs
Coding: c.908del
MANE Select: NM_005612
dbSNP: rs2475825927
Type: Deletion
Location: chr4:56919794 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.53 · 3 PDB
Residue 303: the 'interaction with zfp90' region

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

Disease context

REST-related disorder

Similar variants

REST p.Gln722_Met737del Uncertain significance ★★ same condition
REST p.Glu748fs Likely pathogenic ★ same condition
REST p.Tyr255fs Likely pathogenic ★ same condition
REST p.Val761_Lys762insTer Likely pathogenic same condition
REST p.Asn1080Ser Uncertain significance ★★ ⚠ same condition
REST p.Ile216fs Uncertain significance ★★ same condition
REST p.Ile448Thr Uncertain significance ★★ ⚠ same condition
REST p.Met785Thr 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/rest-p-pro303fs (accessed [today's date]).

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