Is PALLD p.Ser6= (c.18C>T) pathogenic?

PALLD p.Ser6= (c.18C>T) is classified Benign in PALLD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-07-07). Common (popmax 22.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with pancreatic cancer, susceptibility to, 1.

What condition is associated with PALLD p.Ser6= (c.18C>T)?

PALLD p.Ser6= (c.18C>T) is associated with pancreatic cancer, susceptibility to, 1, pancreatic adenocarcinoma (ClinVar).

PALLD p.Ser6=

Q: How common is PALLD p.Ser6= (c.18C>T) in the general population?

PALLD p.Ser6= (c.18C>T) is common (popmax 22.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.18C>T · rs61051061 · VCV348025

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 22.6%, afr) — 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 0.28	GERP -0.34, phastCons 0.98
Overall
CADD	5.001	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 22.6% African / African-American · 16,902/74,926 alleles

Filtering AF 22.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.2%

Overall 20% 322,367/1,612,184 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	24.1%	4
African / African-Americangrpmax	22.6%	4
European (non-Finnish)	20.4%	5
Finnishnot grpmax-eligible	20%	5
Remaining individualsnot grpmax-eligible	20%	5
Middle Eastern	20%	5
East Asian	19.2%	5
Admixed American	16.3%	6
Amishnot grpmax-eligible	15.8%	6
South Asian	13.5%	7

Ashkenazi Jewish 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.Ser6=
Coding: c.18C>T
MANE Select: NM_001166108
dbSNP: rs61051061
Type: single nucleotide variant
Location: chr4:168511522 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB
Residue 6: 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

Also linked: pancreatic adenocarcinoma

Similar variants

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
PALLD c.1965-12552G>C Uncertain significance ★★ same condition
PALLD c.1965-12553G>A 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-ser6 (accessed [today's date]).

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