Is PALLD p.Lys377Glu (c.1129A>G) pathogenic?

PALLD p.Lys377Glu (c.1129A>G) is classified Uncertain significance in PALLD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-26). Ultra-rare (popmax 0.0103%, nfe); Associated with pancreatic cancer, susceptibility to, 1.

What condition is associated with PALLD p.Lys377Glu (c.1129A>G)?

PALLD p.Lys377Glu (c.1129A>G) is associated with pancreatic cancer, susceptibility to, 1 (ClinVar).

How common is PALLD p.Lys377Glu (c.1129A>G) in the general population?

PALLD p.Lys377Glu (c.1129A>G) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

PALLD p.Lys377Glu

c.1129A>G · rs368684220 · VCV902977

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, 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	0.085	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -4.5, phastCons 0.14
Regional constraint	o/e 0.99	unconstrained · MANE · 387 kb · p 0.73 · regional, not allelic
Overall
CADD	16.51	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 121/1,175,678 alleles

Filtering AF 0.00879% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00823%

Overall 0.00758% 122/1,609,002 alleles · ultra-rare exomes 119/1,456,840 · genomes 3/152,162 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,716
African / African-American	0.00134%	74,818

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.Lys377Glu
Coding: c.1129A>G
MANE Select: NM_001166108
dbSNP: rs368684220
Type: single nucleotide variant
Location: chr4:168681373 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB

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.Lys377Ile Uncertain significance ★ same residue
PALLD p.Lys377= Likely benign ★ 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

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-lys377glu (accessed [today's date]).

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