Is EPPK1 p.Ser2244= (c.6732C>T) pathogenic?

EPPK1 p.Ser2244= (c.6732C>T) is classified Likely benign in EPPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). Very rare (popmax 0.000317%); Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Ser2244= (c.6732C>T)?

EPPK1 p.Ser2244= (c.6732C>T) is associated with EPPK1-related disorder (ClinVar).

How common is EPPK1 p.Ser2244= (c.6732C>T) in the general population?

EPPK1 p.Ser2244= (c.6732C>T) is very rare (popmax 0.000317%) (gnomAD).

EPPK1 p.Ser2244=

c.6732C>T · rs1819111498 · VCV3052691

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000317%)

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 -2.6	GERP 0.52
Overall
CADD	12.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000317%

Overall 0.000317% 5/1,575,566 alleles · very rare

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.Ser2244=
Coding: c.6732C>T
MANE Select: NM_031308
dbSNP: rs1819111498
Type: single nucleotide variant
Location: chr8:143866522 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 2244: 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.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
EPPK1 p.Arg2356= 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-ser2244 (accessed [today's date]).

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