Is ADPRS p.Arg286His (c.857G>A) pathogenic?

ADPRS p.Arg286His (c.857G>A) is classified Uncertain significance in ADPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-19). AlphaMissense: likely benign (0.1608); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Arg286His (c.857G>A)?

ADPRS p.Arg286His (c.857G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Arg286His (c.857G>A) in the general population?

ADPRS p.Arg286His (c.857G>A) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about ADPRS p.Arg286His (c.857G>A)?

AlphaMissense predicts likely benign (score 0.1608) — an in-silico prediction, not a clinical call.

ADPRS p.Arg286His

c.857G>A · VCV4245216

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1608 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1608	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	LLR -10.58	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 0.85, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	23.6	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

Grpmax group 0.00144% European (non-Finnish) · 17/1,180,058 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.00118% 19/1,614,064 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,488
European (non-Finnish)grpmax	0.00144%	69,415
South Asian	0.0011%	91,088

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ADPRS
Protein: p.Arg286His
Coding: c.857G>A
MANE Select: NM_017825
Type: single nucleotide variant
Location: chr1:36093151 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 286: a UniProt-annotated variant site (in condsias; no detectable protein in patient fibroblasts); an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADPRS p.Arg286Cys Uncertain significance ★ ⚠ same residue
ADPRS p.Ala94Asp Uncertain significance ★★ ⚠ same condition
ADPRS p.Ala5Val Likely benign ★★ same condition
ADPRS c.517-4C>G Uncertain significance ★ same condition
ADPRS p.Ala101Thr Uncertain significance ★ ⚠ same condition
ADPRS p.Ala14Pro Uncertain significance ★ ⚠ same condition
ADPRS p.Ala16Gly Uncertain significance ★ ⚠ same condition
ADPRS p.Ala191Thr 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/adprs-p-arg286his (accessed [today's date]).

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