Is EPPK1 p.Asp368Glu (c.1104C>G) pathogenic?

EPPK1 p.Asp368Glu (c.1104C>G) is classified Uncertain significance in EPPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.8503); Very rare (popmax 0.00825%, nfe).

How common is EPPK1 p.Asp368Glu (c.1104C>G) in the general population?

EPPK1 p.Asp368Glu (c.1104C>G) is very rare (popmax 0.00825%, nfe) (gnomAD).

What do computational predictors say about EPPK1 p.Asp368Glu (c.1104C>G)?

AlphaMissense predicts likely pathogenic (score 0.8503) — an in-silico prediction, not a clinical call.

EPPK1 p.Asp368Glu

c.1104C>G · rs782321412 · VCV2595876

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8503 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00825%, nfe)

Computational evidence

Protein change
AlphaMissense	0.8503	likely pathogenic
REVEL	0.348	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP -0.63, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 7,913 bp · p 8.9e-24 · regional, not allelic
Overall
CADD	15.22	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00825% European (non-Finnish) · 96/1,163,918 alleles

Filtering AF 0.0069% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.0062% 98/1,581,076 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00825%	12,124
Remaining individualsnot grpmax-eligible	0.00164%	60,946
African / African-American	0.00135%	74,292

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.Asp368Glu
Coding: c.1104C>G
MANE Select: NM_031308
dbSNP: rs782321412
Type: single nucleotide variant
Location: chr8:143872150 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 368: the 'interaction with krt5' region

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

Similar variants

EPPK1 p.Gly716Ser Uncertain significance ★★ same type
EPPK1 p.Gly441Ser Benign/Likely benign ★★ same type
EPPK1 p.Ala1025Thr Uncertain significance ★ same type
EPPK1 p.Ala1076Val Uncertain significance ★ ⚠ same type
EPPK1 p.Ala1119Val Uncertain significance ★ ⚠ same type
EPPK1 p.Ala1138Val Uncertain significance ★ ⚠ same type
EPPK1 p.Ala118Thr Uncertain significance ★ same type
EPPK1 p.Ala1205Thr Uncertain significance ★ ⚠ same type

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-asp368glu (accessed [today's date]).

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