Is PRUNE1 p.Pro353Arg (c.1058C>G) pathogenic?

PRUNE1 p.Pro353Arg (c.1058C>G) is classified Benign/Likely benign in PRUNE1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-03-01). AlphaMissense: ambiguous (0.5233); Rare (popmax 0.636%, nfe).

How common is PRUNE1 p.Pro353Arg (c.1058C>G) in the general population?

PRUNE1 p.Pro353Arg (c.1058C>G) is rare (popmax 0.636%, nfe) (gnomAD).

What do computational predictors say about PRUNE1 p.Pro353Arg (c.1058C>G)?

AlphaMissense predicts ambiguous (score 0.5233) — an in-silico prediction, not a clinical call.

PRUNE1 p.Pro353Arg

c.1058C>G · rs72706548 · VCV2049102

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.5233 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.636%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5233	ambiguous
REVEL	0.578	indeterminate
SaProt	LLR -15.19	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 26 kb · p 3.4e-05 · regional, not allelic
Overall
CADD	25.6	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 0.636% European (non-Finnish) · 7,509/1,179,970 alleles

Filtering AF 0.624% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.619%

Overall 0.511% 8,244/1,614,062 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.636%	157
Remaining individualsnot grpmax-eligible	0.413%	242
Ashkenazi Jewishnot grpmax-eligible	0.388%	257
Finnishnot grpmax-eligible	0.255%	393
African / African-American	0.0933%	1,072
South Asian	0.0845%	1,183
Middle Eastern	0.0825%	1,212
Admixed American	0.0783%	1,277

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: PRUNE1
Protein: p.Pro353Arg
Coding: c.1058C>G
MANE Select: NM_021222
dbSNP: rs72706548
Type: single nucleotide variant
Location: chr1:151033930 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.61
Residue 353: a UniProt-annotated variant site (in nmihba)

Full PRUNE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRUNE1 c.132+2T>C Pathogenic ★★ same type
PRUNE1 c.521-2A>G Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Arg128Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
PRUNE1 p.Arg66Ter Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Asp106Asn Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Asp30Asn Pathogenic/Likely pathogenic ★★ same type
PRUNE1 p.Ala39Pro Uncertain significance ★★ ⚠ same type
PRUNE1 p.Asp87Asn 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/prune1-p-pro353arg (accessed [today's date]).

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