Is PARN p.Val297Phe (c.889G>T) pathogenic?

PARN p.Val297Phe (c.889G>T) is classified Uncertain significance in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-18). AlphaMissense: ambiguous (0.4588); Absent from gnomAD v4.1; Associated with PARN-related disorder.

What condition is associated with PARN p.Val297Phe (c.889G>T)?

PARN p.Val297Phe (c.889G>T) is associated with PARN-related disorder (ClinVar).

How common is PARN p.Val297Phe (c.889G>T) in the general population?

PARN p.Val297Phe (c.889G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PARN p.Val297Phe (c.889G>T)?

AlphaMissense predicts ambiguous (score 0.4588) — an in-silico prediction, not a clinical call.

PARN p.Val297Phe

c.889G>T · rs1230931001 · VCV2636396

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4588 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

PARN-related disorder

Computational evidence

Protein change
AlphaMissense	0.4588	ambiguous
REVEL	0.229	benign-leaning
SaProt	LLR -11.16	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -1, phastCons 0.03
Regional constraint	o/e 1.03	unconstrained · MANE · 193 kb · p 0.44 · regional, not allelic
Overall
CADD	18.87	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: PARN
Protein: p.Val297Phe
Coding: c.889G>T
MANE Select: NM_002582
dbSNP: rs1230931001
Type: single nucleotide variant
Location: chr16:14593330 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 297: an α-helix

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

Disease context

PARN-related disorder

Similar variants

PARN p.Val297Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
PARN p.Arg237Ter Pathogenic/Likely pathogenic ★★ same condition
PARN p.Asp122His Uncertain significance ★★ ⚠ same condition
PARN c.1193-1G>C Likely pathogenic ★ same condition
PARN c.620+1G>T Likely pathogenic ★ same condition
PARN p.Arg150Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
PARN p.Tyr91Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
PARN p.Glu189Ter Likely pathogenic 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/parn-p-val297phe (accessed [today's date]).

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