Is EPPK1 p.Pro1087= (c.3261G>A) pathogenic?

EPPK1 p.Pro1087= (c.3261G>A) is classified Benign in EPPK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-12). Common (popmax 57.2%, mid) — too common for a highly-penetrant pathogenic allele; Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Pro1087= (c.3261G>A)?

EPPK1 p.Pro1087= (c.3261G>A) is associated with EPPK1-related disorder (ClinVar).

EPPK1 p.Pro1087=

Q: How common is EPPK1 p.Pro1087= (c.3261G>A) in the general population?

EPPK1 p.Pro1087= (c.3261G>A) is common (popmax 57.2%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3261G>A · rs35221054 · VCV3035506

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 57.2%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

EPPK1-related disorder

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 -15	GERP -3.6
Overall
CADD	0.083	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.2% Middle Eastern · 3,446/6,026 alleles

Filtering AF 55.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 54.9%

Overall 45.1% 724,072/1,605,686 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	63.4%	2
Middle Easterngrpmax	57.2%	2
Amishnot grpmax-eligible	55.8%	2
European (non-Finnish)	47.8%	2
South Asian	46.7%	2
Remaining individualsnot grpmax-eligible	44.1%	2
Admixed American	44%	2
Finnishnot grpmax-eligible	42%	2
East Asian	25.9%	4
African / African-American	8.65%	12

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: EPPK1
Protein: p.Pro1087=
Coding: c.3261G>A
MANE Select: NM_031308
dbSNP: rs35221054
Type: single nucleotide variant
Location: chr8:143869993 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 1087: the 'interaction with krt5' region

Full EPPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EPPK1-related disorder

Similar variants

EPPK1 p.Pro1087Arg Uncertain significance ★ ⚠ same residue
EPPK1 p.Gln2020Arg Uncertain significance ★ ⚠ same condition
EPPK1 p.Glu140Ter Uncertain significance ★ same condition
EPPK1 p.Pro35Thr Uncertain significance ★ ⚠ same condition
EPPK1 p.Val104Leu Uncertain significance ★ same condition
EPPK1 p.Ala2265= Likely benign ★ same condition
EPPK1 p.Arg2218= Likely benign ★ same condition
EPPK1 p.Arg2305= Likely benign ★ 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/eppk1-p-pro1087 (accessed [today's date]).

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