Is PALLD p.Pro101Ser (c.301C>T) pathogenic?

PALLD p.Pro101Ser (c.301C>T) is classified Uncertain significance in PALLD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-15). Ultra-rare (popmax 0.0165%, mid); Associated with pancreatic cancer, susceptibility to, 1.

What condition is associated with PALLD p.Pro101Ser (c.301C>T)?

PALLD p.Pro101Ser (c.301C>T) is associated with pancreatic cancer, susceptibility to, 1 (ClinVar).

How common is PALLD p.Pro101Ser (c.301C>T) in the general population?

PALLD p.Pro101Ser (c.301C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PALLD p.Pro101Ser

c.301C>T · VCV3590441

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

pancreatic cancer, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.059	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.7	GERP -1.5
Regional constraint	o/e 0.99	unconstrained · MANE · 387 kb · p 0.73 · regional, not allelic
Overall
CADD	1.081	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,614,198 alleles · ultra-rare exomes 5/1,461,868 · genomes 0/152,330 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
European (non-Finnish)	0.000339%	295,010

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: PALLD
Protein: p.Pro101Ser
Coding: c.301C>T
MANE Select: NM_001166108
Type: single nucleotide variant
Location: chr4:168511805 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB
Residue 101: the 'disordered' region

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

Disease context

pancreatic cancer, susceptibility to, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PALLD p.Pro101Leu Uncertain significance ★ same residue
PALLD c.*108C>T Uncertain significance ★★ same condition
PALLD p.Arg272Gln Uncertain significance ★★ same condition
PALLD p.Arg287Gln Uncertain significance ★★ same condition
PALLD p.Arg379Gly Uncertain significance ★★ same condition
PALLD p.Arg524Ile Uncertain significance ★★ same condition
PALLD p.Arg686Gln Uncertain significance ★★ same condition
PALLD p.Arg876His 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-pro101ser (accessed [today's date]).

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