Is EPPK1 p.Asp440= (c.1320C>T) pathogenic?

EPPK1 p.Asp440= (c.1320C>T) is classified Likely benign in EPPK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-18). Rare (popmax 0.509%, afr); Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Asp440= (c.1320C>T)?

EPPK1 p.Asp440= (c.1320C>T) is associated with EPPK1-related disorder (ClinVar).

How common is EPPK1 p.Asp440= (c.1320C>T) in the general population?

EPPK1 p.Asp440= (c.1320C>T) is rare (popmax 0.509%, afr) (gnomAD).

EPPK1 p.Asp440=

c.1320C>T · rs369399530 · VCV3053411

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.509%, afr)

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 0.26	GERP 1.8, phastCons 0.93
Overall
CADD	7.737	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.509% African / African-American · 382/75,008 alleles

Filtering AF 0.467% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.451%

Overall 0.0303% 486/1,602,798 alleles · rare exomes 256/1,450,446 · genomes 230/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.509%	196
Admixed American	0.0569%	1,758
Middle Eastern	0.0499%	2,006
Remaining individualsnot grpmax-eligible	0.0466%	2,145
South Asian	0.00771%	12,968
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,743
East Asian	0.00446%	22,397
European (non-Finnish)	0.00221%	45,341
Finnishnot grpmax-eligible	0.00182%	54,960

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.Asp440=
Coding: c.1320C>T
MANE Select: NM_031308
dbSNP: rs369399530
Type: single nucleotide variant
Location: chr8:143871934 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 440: 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-asp440 (accessed [today's date]).

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