Is ADPRS p.Arg240His (c.719G>A) pathogenic?

ADPRS p.Arg240His (c.719G>A) is classified Conflicting classifications of pathogenicity in ADPRS (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-20). AlphaMissense: likely benign (0.0768); Ultra-rare (popmax 0.0176%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Arg240His (c.719G>A)?

ADPRS p.Arg240His (c.719G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Arg240His (c.719G>A) in the general population?

ADPRS p.Arg240His (c.719G>A) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

What do computational predictors say about ADPRS p.Arg240His (c.719G>A)?

AlphaMissense predicts likely benign (score 0.0768) — an in-silico prediction, not a clinical call.

ADPRS p.Arg240His

c.719G>A · rs148612837 · VCV2564423

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0768 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0768	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -3.6, phastCons 0.46
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	16.37	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 0.0176% European (non-Finnish) · 208/1,180,018 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.0136% 219/1,614,034 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0176%	5,673
Remaining individualsnot grpmax-eligible	0.0096%	10,414
East Asian	0.00668%	14,964
African / African-American	0.00267%	37,458

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.Arg240His
Coding: c.719G>A
MANE Select: NM_017825
dbSNP: rs148612837
Type: single nucleotide variant
Location: chr1:36092439 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 240: a UniProt-annotated variant site (in condsias; no detectable protein in patient fibroblasts)

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.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
ADPRS p.Ala195Ser 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-arg240his (accessed [today's date]).

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