Is PRUNE1 p.Leu270Pro (c.809T>C) pathogenic?

PRUNE1 p.Leu270Pro (c.809T>C) is classified Likely pathogenic in PRUNE1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-13). AlphaMissense: likely pathogenic (0.9737); Absent from gnomAD v4.1.

How common is PRUNE1 p.Leu270Pro (c.809T>C) in the general population?

PRUNE1 p.Leu270Pro (c.809T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRUNE1 p.Leu270Pro (c.809T>C)?

AlphaMissense predicts likely pathogenic (score 0.9737) — an in-silico prediction, not a clinical call.

PRUNE1 p.Leu270Pro

c.809T>C · rs1553254265 · VCV450387

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9737 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9737	likely pathogenic ✓ concordant with ClinVar · top 3% in PRUNE1
REVEL	0.455	indeterminate
SaProt	LLR -15.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 26 kb · p 3.4e-05 · regional, not allelic
Overall
CADD	25.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRUNE1
Protein: p.Leu270Pro
Coding: c.809T>C
MANE Select: NM_021222
dbSNP: rs1553254265
Type: single nucleotide variant
Location: chr1:151028820 (GRCh38)
Gene constraint: LOEUF 0.902 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.61
Residue 270: 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-leu270pro (accessed [today's date]).

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