Is REST p.Val897= (c.2691A>G) pathogenic?

REST p.Val897= (c.2691A>G) is classified Likely benign in REST (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-19). Absent from gnomAD v4.1.

How common is REST p.Val897= (c.2691A>G) in the general population?

REST p.Val897= (c.2691A>G) is absent from gnomAD v4.1 (gnomAD).

REST p.Val897=

c.2691A>G · rs2475854009 · VCV2008379

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.66	GERP -3.9
Overall
CADD	2.165	PHRED · no single calibrated threshold — expert panels disagree

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: REST
Protein: p.Val897=
Coding: c.2691A>G
MANE Select: NM_005612
dbSNP: rs2475854009
Type: single nucleotide variant
Location: chr4:56931549 (GRCh38)
Gene constraint: LOEUF 0.16 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.53 · 3 PDB
Residue 897: the 'disordered' region; a UniProt-annotated variant site (in gingf5)

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

Similar variants

REST p.Val897Ile Uncertain significance ★★ ⚠ same residue
REST p.Ala198Val Uncertain significance ★★ ⚠ same type
REST p.Ala25Ser Uncertain significance ★★ ⚠ same type
REST p.Ala637Ser Uncertain significance ★★ ⚠ same type
REST p.Ala642Val Uncertain significance ★★ ⚠ same type
REST p.Ala678Ser Uncertain significance ★★ ⚠ same type
REST p.Ala998Thr Uncertain significance ★★ ⚠ same type
REST p.Arg199Gly Uncertain significance ★★ ⚠ 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-val897 (accessed [today's date]).

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