Is PLAUR p.Ile85Val (c.253A>G) pathogenic?

PLAUR p.Ile85Val (c.253A>G) is classified Uncertain significance in PLAUR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: ambiguous (0.3406); Absent from gnomAD v4.1.

How common is PLAUR p.Ile85Val (c.253A>G) in the general population?

PLAUR p.Ile85Val (c.253A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PLAUR p.Ile85Val (c.253A>G)?

AlphaMissense predicts ambiguous (score 0.3406) — an in-silico prediction, not a clinical call.

PLAUR p.Ile85Val

c.253A>G · VCV3419880

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3406 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3406	ambiguous
REVEL	0.119	moderately benign-leaning
SaProt	LLR -5.43	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.4	GERP 0.96, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 21 kb · p 0.2 · regional, not allelic
Overall
CADD	14.25	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: PLAUR
Protein: p.Ile85Val
Coding: c.253A>G
MANE Select: NM_002659
Type: single nucleotide variant
Location: chr19:43665373 (GRCh38)
Gene constraint: LOEUF 0.911 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.56 · 13 PDB
Residue 85: the upar/ly6 1 domain; a β-strand

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

Similar variants

PLAUR p.Ile85Thr Uncertain significance ★ ⚠ same residue
PLAUR p.His251= Likely benign ★★ same type
PLAUR p.Met268Val Likely benign ★★ same type
PLAUR p.Pro8= Benign/Likely benign ★★ same type
PLAUR p.Ala106Asp Uncertain significance ★ ⚠ same type
PLAUR p.Arg113Cys Uncertain significance ★ ⚠ same type
PLAUR p.Arg113His Uncertain significance ★ ⚠ same type
PLAUR p.Arg131Gly 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/plaur-p-ile85val (accessed [today's date]).

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