Is EPPK1 p.Phe2368= (c.7104C>T) pathogenic?

EPPK1 p.Phe2368= (c.7104C>T) is classified Likely benign in EPPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-30). Ultra-rare (popmax 0.0937%, nfe); Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Phe2368= (c.7104C>T)?

EPPK1 p.Phe2368= (c.7104C>T) is associated with EPPK1-related disorder (ClinVar).

How common is EPPK1 p.Phe2368= (c.7104C>T) in the general population?

EPPK1 p.Phe2368= (c.7104C>T) is ultra-rare (popmax 0.0937%, nfe) (gnomAD).

EPPK1 p.Phe2368=

c.7104C>T · rs1320140952 · VCV3055080

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0937%, nfe)

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 -20	GERP -3.6
Overall
CADD	6.779	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0937% European (non-Finnish) · 215/229,342 alleles

Filtering AF 0.0834% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0795%

Overall 0.0714% 273/382,478 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0937%	1,067
Remaining individualsnot grpmax-eligible	0.0853%	1,172
Finnishnot grpmax-eligible	0.0834%	1,199
East Asian	0.0399%	2,505
Admixed American	0.0335%	2,984
African / African-American	0.00911%	10,974
Ashkenazi Jewishnot grpmax-eligible	0.00844%	11,854
South Asian	0.00234%	42,660

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.Phe2368=
Coding: c.7104C>T
MANE Select: NM_031308
dbSNP: rs1320140952
Type: single nucleotide variant
Location: chr8:143866150 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 2368: 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-phe2368 (accessed [today's date]).

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