Is PALLD p.Arg303Ser (c.909A>T) pathogenic?

PALLD p.Arg303Ser (c.909A>T) is classified Conflicting classifications of pathogenicity in PALLD (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2022-03-01). Ultra-rare (popmax 0.058%, nfe); Associated with pancreatic cancer, susceptibility to, 1.

What condition is associated with PALLD p.Arg303Ser (c.909A>T)?

PALLD p.Arg303Ser (c.909A>T) is associated with pancreatic cancer, susceptibility to, 1 (ClinVar).

How common is PALLD p.Arg303Ser (c.909A>T) in the general population?

PALLD p.Arg303Ser (c.909A>T) is ultra-rare (popmax 0.058%, nfe) (gnomAD).

PALLD p.Arg303Ser

c.909A>T · rs138897963 · VCV128115

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.058%, nfe)

Conditions

pancreatic cancer, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.375	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -4.2, phastCons 0.99
Regional constraint	o/e 0.99	unconstrained · MANE · 387 kb · p 0.73 · regional, not allelic
Overall
CADD	21.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.058% European (non-Finnish) · 684/1,179,508 alleles

Filtering AF 0.0543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0529%

Overall 0.0693% 1,119/1,613,570 alleles · ultra-rare exomes 961/1,461,322 · genomes 158/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.59%	169
Remaining individualsnot grpmax-eligible	0.064%	1,562
European (non-Finnish)grpmax	0.058%	1,724
Admixed American	0.02%	5,001
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,803
African / African-American	0.004%	25,009

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg303Ser
Coding: c.909A>T
MANE Select: NM_001166108
dbSNP: rs138897963
Type: single nucleotide variant
Location: chr4:168668190 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB
Residue 303: the ig-like c2-type 1 domain

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.Arg303Gly 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-arg303ser (accessed [today's date]).

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