Is EPPK1 p.Ala2001= (c.6003G>A) pathogenic?

EPPK1 p.Ala2001= (c.6003G>A) is classified Benign in EPPK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-04-12). Common (popmax 40.3%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Ala2001= (c.6003G>A)?

EPPK1 p.Ala2001= (c.6003G>A) is associated with EPPK1-related disorder (ClinVar).

EPPK1 p.Ala2001=

Q: How common is EPPK1 p.Ala2001= (c.6003G>A) in the general population?

EPPK1 p.Ala2001= (c.6003G>A) is common (popmax 40.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6003G>A · rs12681478 · VCV3035773

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 40.3%, nfe) — 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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Overall
CADD	3.544	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 40.3% European (non-Finnish) · 474,950/1,179,468 alleles

Filtering AF 40.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 40.1%

Overall 36.9% 595,029/1,611,972 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	40.3%	2
Finnishnot grpmax-eligible	38.5%	3
Ashkenazi Jewishnot grpmax-eligible	38%	3
Amishnot grpmax-eligible	35.9%	3
Middle Eastern	35.2%	3
Remaining individualsnot grpmax-eligible	34.8%	3
South Asian	33.7%	3
Admixed American	32.2%	3
East Asian	11.3%	9
African / African-American	7.25%	14

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.Ala2001=
Coding: c.6003G>A
MANE Select: NM_031308
dbSNP: rs12681478
Type: single nucleotide variant
Location: chr8:143867251 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 2001: 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.Ala2001Val 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-ala2001 (accessed [today's date]).

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