Is REST p.Pro142fs (c.425del) pathogenic?

REST p.Pro142fs (c.425del) is classified Pathogenic in REST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-29). No gnomAD frequency available for this variant.

How common is REST p.Pro142fs (c.425del) in the general population?

REST p.Pro142fs (c.425del) is no gnomAD frequency available for this variant (gnomAD).

REST p.Pro142fs

c.425del · rs2109523966 · VCV1423378

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.15	GERP -4.1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Pro142fs
Coding: c.425del
MANE Select: NM_005612
dbSNP: rs2109523966
Type: Deletion
Location: chr4:56911059 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.53 · 3 PDB
Residue 142: the 'disordered' region

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

Similar variants

REST p.Pro142Arg Uncertain significance ★★ ⚠ same residue
REST p.Pro142= Likely benign ★ same residue
REST p.Gln722_Met737del Uncertain significance ★★ same type
REST p.Met753_Pro768del Uncertain significance ★★ same type
REST p.Gln746_Val761del Benign ★★ same type
REST p.Asn385fs Likely pathogenic ★ same type
REST p.Asn59fs Pathogenic ★ same type
REST p.Cys278fs Pathogenic ★ same type

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-pro142fs (accessed [today's date]).

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