Is PALLD p.Arg689Pro (c.2066G>C) pathogenic?

PALLD p.Arg689Pro (c.2066G>C) is classified Uncertain significance in PALLD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-01). Absent from gnomAD v4.1; Associated with pancreatic adenocarcinoma.

What condition is associated with PALLD p.Arg689Pro (c.2066G>C)?

PALLD p.Arg689Pro (c.2066G>C) is associated with pancreatic adenocarcinoma (ClinVar).

How common is PALLD p.Arg689Pro (c.2066G>C) in the general population?

PALLD p.Arg689Pro (c.2066G>C) is absent from gnomAD v4.1 (gnomAD).

PALLD p.Arg689Pro

c.2066G>C · rs758090588 · VCV1716363

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pancreatic adenocarcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.569	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 387 kb · p 0.73 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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: PALLD
Protein: p.Arg689Pro
Coding: c.2066G>C
MANE Select: NM_001166108
dbSNP: rs758090588
Type: single nucleotide variant
Location: chr4:168891023 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB
Residue 689: the 'disordered' region; the 'interaction with sorbs2, spin90 and src' region

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

Disease context

pancreatic adenocarcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PALLD p.Arg689Cys Uncertain significance ★★ same residue
PALLD p.Arg689His Uncertain significance ★★ same residue
PALLD c.1965-12532C>A Uncertain significance ★★ same condition
PALLD c.1965-12532C>G Uncertain significance ★★ same condition
PALLD c.1965-12534C>A Uncertain significance ★★ same condition
PALLD c.1965-12535A>C Uncertain significance ★★ same condition
PALLD c.1965-12544A>G Uncertain significance ★★ same condition
PALLD c.1965-12549T>C 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/palld-p-arg689pro (accessed [today's date]).

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