Is ADPRS p.Pro60Arg (c.179C>G) pathogenic?

ADPRS p.Pro60Arg (c.179C>G) is classified Uncertain significance in ADPRS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.0874); Ultra-rare (popmax 0.018%, afr); Associated with Inborn genetic diseases.

What condition is associated with ADPRS p.Pro60Arg (c.179C>G)?

ADPRS p.Pro60Arg (c.179C>G) is associated with Inborn genetic diseases (ClinVar).

How common is ADPRS p.Pro60Arg (c.179C>G) in the general population?

ADPRS p.Pro60Arg (c.179C>G) is ultra-rare (popmax 0.018%, afr) (gnomAD).

What do computational predictors say about ADPRS p.Pro60Arg (c.179C>G)?

AlphaMissense predicts likely benign (score 0.0874) — an in-silico prediction, not a clinical call.

ADPRS p.Pro60Arg

c.179C>G · VCV3838910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0874 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.018%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0874	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.37	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 4.6	GERP 0.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 4,478 bp · p 0.95 · regional, not allelic
Overall
CADD	20.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.018% African / African-American · 12/66,666 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00805%

Overall 0.00132% 19/1,434,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.018%	5,555
Admixed American	0.00933%	10,713
Remaining individualsnot grpmax-eligible	0.00733%	13,646

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.Pro60Arg
Coding: c.179C>G
MANE Select: NM_017825
Type: single nucleotide variant
Location: chr1:36089083 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.70 · 14 PDB
Residue 60: 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.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-pro60arg (accessed [today's date]).

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