Is RGR p.Asp86fs (c.250_257dup) pathogenic?

RGR p.Asp86fs (c.250257dup) is classified Uncertain significance in RGR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-27). Very rare (popmax 0.005%, amr).

How common is RGR p.Asp86fs (c.250_257dup) in the general population?

RGR p.Asp86fs (c.250_257dup) is very rare (popmax 0.005%, amr) (gnomAD).

RGR p.Asp86fs

c.250_257dup · rs1564548704 · VCV967356

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -7.9	GERP -3.6
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,004 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000186% 3/1,614,008 alleles · very rare exomes 2/1,461,784 · genomes 1/152,224 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: RGR
Protein: p.Asp86fs
Coding: c.250_257dup
MANE Select: NM_001012720
dbSNP: rs1564548704
Type: Duplication
Location: chr10:84248934 (GRCh38)
Structure: AlphaFold pLDDT 62.88

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

Similar variants

RGR p.Asp86= Likely benign ★★ same residue
RGR p.Asp86Gly Uncertain significance ★ ⚠ same residue
RGR p.Ile263fs Uncertain significance ★★ same type
RGR p.Ile276fs Conflicting classifications of pathogenicity ★ same type
RGR c.*74dup 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/rgr-p-asp86fs (accessed [today's date]).

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