Is PARN p.Phe69Leu (c.207T>G) pathogenic?

PARN p.Phe69Leu (c.207T>G) is classified Uncertain significance in PARN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.9856); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PARN p.Phe69Leu (c.207T>G)?

PARN p.Phe69Leu (c.207T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PARN p.Phe69Leu (c.207T>G) in the general population?

PARN p.Phe69Leu (c.207T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PARN p.Phe69Leu (c.207T>G)?

AlphaMissense predicts likely pathogenic (score 0.9856) — an in-silico prediction, not a clinical call.

PARN p.Phe69Leu

c.207T>G · rs2508628290 · VCV2264989

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9856 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9856	likely pathogenic
REVEL	0.219	benign-leaning
SaProt	LLR -10.28	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.2	phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 193 kb · p 0.44 · regional, not allelic
Overall
CADD	25.1	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.Phe69Leu
Coding: c.207T>G
MANE Select: NM_002582
dbSNP: rs2508628290
Type: single nucleotide variant
Location: chr16:14627307 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.60 · 3 PDB
Residue 69: a β-strand

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PARN p.Arg140Gly Uncertain significance ★★ ⚠ same condition
PARN p.Arg249His Uncertain significance ★★ ⚠ same condition
PARN p.Arg538Pro Uncertain significance ★★ ⚠ same condition
PARN p.Arg554Cys Uncertain significance ★★ ⚠ same condition
PARN p.Arg99Thr Uncertain significance ★★ ⚠ same condition
PARN p.Asp477Gly Uncertain significance ★★ same condition
PARN p.Asp595Tyr Uncertain significance ★★ ⚠ same condition
PARN p.Glu52Asp Uncertain significance ★★ ⚠ 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-phe69leu (accessed [today's date]).

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