Is PALLD p.Ala509= (c.1527T>G) pathogenic?

PALLD p.Ala509= (c.1527T>G) is classified Benign in PALLD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2023-07-07). Common (popmax 28.4%, eas) — too common for a highly-penetrant pathogenic allele; Associated with pancreatic cancer, susceptibility to, 1.

What condition is associated with PALLD p.Ala509= (c.1527T>G)?

PALLD p.Ala509= (c.1527T>G) is associated with pancreatic cancer, susceptibility to, 1 (ClinVar).

PALLD p.Ala509=

Q: How common is PALLD p.Ala509= (c.1527T>G) in the general population?

PALLD p.Ala509= (c.1527T>G) is common (popmax 28.4%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1527T>G · rs58395080 · VCV348040

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 28.4%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

pancreatic cancer, susceptibility to, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -4.3
Overall
CADD	0.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 28.4% East Asian · 12,740/44,848 alleles

Filtering AF 28% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.8%

Overall 1.44% 23,179/1,613,366 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	28.4%	4
African / African-American	3.86%	26
Remaining individualsnot grpmax-eligible	2.03%	49
Admixed American	1.33%	75
Finnishnot grpmax-eligible	0.964%	104
South Asian	0.896%	112
Middle Eastern	0.825%	121
European (non-Finnish)	0.332%	301
Ashkenazi Jewishnot grpmax-eligible	0.253%	395
Amishnot grpmax-eligible	0.11%	912

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.Ala509=
Coding: c.1527T>G
MANE Select: NM_001166108
dbSNP: rs58395080
Type: single nucleotide variant
Location: chr4:168709053 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB
Residue 509: the ig-like c2-type 2 domain; a disulfide bond

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.Ala509Ser Uncertain significance ★ same residue
PALLD p.Ala509Thr Uncertain significance ★ same residue
PALLD p.Ala509Val 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

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-ala509 (accessed [today's date]).

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