Is PRKN p.Val3Glu (c.8T>A) pathogenic?

PRKN p.Val3Glu (c.8T>A) is classified Likely pathogenic in PRKN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-10). AlphaMissense: likely pathogenic (0.8562); Very rare (popmax 0.00223%, eas).

How common is PRKN p.Val3Glu (c.8T>A) in the general population?

PRKN p.Val3Glu (c.8T>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PRKN p.Val3Glu (c.8T>A)?

AlphaMissense predicts likely pathogenic (score 0.8562) — an in-silico prediction, not a clinical call.

PRKN p.Val3Glu

c.8T>A · VCV3381019

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8562 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8562	likely pathogenic ✓ concordant with ClinVar
REVEL	0.914	moderately pathogenic-leaning
SaProt	LLR -14.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.23	acceptor loss, 10 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 1,378 kb · p 0.013 · regional, not allelic
Overall
CADD	32.0	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 0.00223% East Asian · 1/44,880 alleles

Overall 6.2e-05% 1/1,613,910 alleles · very rare exomes 0/1,461,712 · genomes 1/152,198 · joint denominator

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: PRKN
Protein: p.Val3Glu
Coding: c.8T>A
MANE Select: NM_004562
Type: single nucleotide variant
Location: chr6:162443473 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.10 · 21 PDB
Residue 3: the ubiquitin-like domain; a β-strand

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

Similar variants

PRKN p.Val3Ala Uncertain significance ★ ⚠ same residue
PRKN p.Arg275Trp Pathogenic/Likely pathogenic ★★ same type
PRKN p.Arg33Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
PRKN p.Arg33Ter Pathogenic ★★ same type
PRKN p.Arg42Pro Pathogenic ★★ same type
PRKN p.Cys212Tyr Pathogenic ★★ same type
PRKN p.Cys253Tyr Pathogenic/Likely pathogenic ★★ same type
PRKN p.Cys268Ter Pathogenic ★★ 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/prkn-p-val3glu (accessed [today's date]).

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