Is ADPRS p.Arg114fs (c.340_341del) pathogenic?

ADPRS p.Arg114fs (c.340341del) is classified Pathogenic in ADPRS (ClinVar, Single submitter, 2 submitters; last evaluated 2026-04-22). Ultra-rare (popmax 0.0152%, amr).

How common is ADPRS p.Arg114fs (c.340_341del) in the general population?

ADPRS p.Arg114fs (c.340_341del) is ultra-rare (popmax 0.0152%, amr) (gnomAD).

ADPRS p.Arg114fs

c.340_341del · rs768832709 · VCV1339799

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, 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	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.7	GERP -1.6, phastCons 1
Overall
CADD	34.0	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 0.0152% Admixed American · 9/59,122 alleles

Filtering AF 0.00794% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00586%

Overall 0.000746% 12/1,608,996 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0152%	6,569
African / African-American	0.00134%	74,820
European (non-Finnish)	0.00017%	588,633

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.Arg114fs
Coding: c.340_341del
MANE Select: NM_017825
dbSNP: rs768832709
Type: Deletion
Location: chr1:36091649 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 114: a UniProt-annotated variant site (in condsias; no detectable protein in patient fibroblasts); a turn

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

Similar variants

ADPRS p.Arg114Ser Uncertain significance ★ ⚠ same residue
ADPRS p.Ala139fs Pathogenic ★★ same type
ADPRS p.Thr49fs Pathogenic ★ same type
ADPRS p.Val98fs Likely pathogenic ★ same type
ADPRS p.Lys248_Ile249delinsAsn Conflicting classifications of pathogenicity ★ same type
ADPRS p.Met332fs Uncertain significance ★ same type
ADPRS p.Lys213fs 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/adprs-p-arg114fs (accessed [today's date]).

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