Is PALLD p.Asp226= (c.678C>T) pathogenic?

PALLD p.Asp226= (c.678C>T) is classified Benign in PALLD (ClinVar, Multiple submitters, 7 submitters; last evaluated 2024-10-28). Common (popmax 32.6%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with pancreatic cancer, susceptibility to, 1.

What condition is associated with PALLD p.Asp226= (c.678C>T)?

PALLD p.Asp226= (c.678C>T) is associated with pancreatic cancer, susceptibility to, 1, pancreatic adenocarcinoma (ClinVar).

PALLD p.Asp226=

Q: How common is PALLD p.Asp226= (c.678C>T) in the general population?

PALLD p.Asp226= (c.678C>T) is common (popmax 32.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.678C>T · rs7673220 · VCV348032

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 32.6%, nfe) — 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 -0.52	GERP -3.2, phastCons 0.003
Overall
CADD	0.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 32.6% European (non-Finnish) · 384,632/1,179,320 alleles

Filtering AF 32.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 32.5%

Overall 30.9% 498,446/1,613,010 alleles · common exomes 453,975/1,461,228 · genomes 44,471/151,782 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	39.3%	3
Amishnot grpmax-eligible	38.8%	3
European (non-Finnish)grpmax	32.6%	3
Remaining individualsnot grpmax-eligible	29.6%	3
Ashkenazi Jewishnot grpmax-eligible	29.6%	3
African / African-American	24.5%	4
Middle Eastern	24.1%	4
South Asian	22.5%	4
Admixed American	20.2%	5
East Asian	19.4%	5

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.Asp226=
Coding: c.678C>T
MANE Select: NM_001166108
dbSNP: rs7673220
Type: single nucleotide variant
Location: chr4:168512182 (GRCh38)
Gene constraint: LOEUF 0.644 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 54.74 · 2 PDB
Residue 226: 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 p.Asp226Glu Uncertain significance ★ same residue
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

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-asp226 (accessed [today's date]).

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