Is ADPRS p.Arg140Trp (c.418C>T) pathogenic?

ADPRS p.Arg140Trp (c.418C>T) is classified Uncertain significance in ADPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-29). AlphaMissense: likely benign (0.2958); Very rare (popmax 0.00801%, afr); Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Arg140Trp (c.418C>T)?

ADPRS p.Arg140Trp (c.418C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Arg140Trp (c.418C>T) in the general population?

ADPRS p.Arg140Trp (c.418C>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about ADPRS p.Arg140Trp (c.418C>T)?

AlphaMissense predicts likely benign (score 0.2958) — an in-silico prediction, not a clinical call.

ADPRS p.Arg140Trp

c.418C>T · VCV4245226

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2958	likely benign
REVEL	0.28	benign-leaning
SaProt	LLR -14.00	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 2.6	GERP 0.68, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	27.5	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 0.00801% African / African-American · 6/74,882 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00174% 28/1,613,622 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00801%	12,480
South Asian	0.00769%	12,998
Admixed American	0.00334%	29,951
Remaining individualsnot grpmax-eligible	0.0032%	31,232
European (non-Finnish)	0.000932%	107,263

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.Arg140Trp
Coding: c.418C>T
MANE Select: NM_017825
Type: single nucleotide variant
Location: chr1:36091727 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 140: 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.Arg140Gln 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-arg140trp (accessed [today's date]).

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