Is EPPK1 p.Arg24= (c.70A>C) pathogenic?

EPPK1 p.Arg24= (c.70A>C) is classified Likely benign in EPPK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-01-14). Rare (popmax 0.163%, eas); Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Arg24= (c.70A>C)?

EPPK1 p.Arg24= (c.70A>C) is associated with EPPK1-related disorder (ClinVar).

How common is EPPK1 p.Arg24= (c.70A>C) in the general population?

EPPK1 p.Arg24= (c.70A>C) is rare (popmax 0.163%, eas) (gnomAD).

EPPK1 p.Arg24=

c.70A>C · rs74594612 · VCV3055106

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.163%, eas)

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 -1	GERP -2.6
Overall
CADD	0.754	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.163% East Asian · 73/44,794 alleles

Filtering AF 0.133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.122%

Overall 0.00764% 122/1,596,086 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.163%	614
Remaining individualsnot grpmax-eligible	0.0712%	1,404
Admixed American	0.00353%	28,353
African / African-American	0.00269%	37,215
European (non-Finnish)	8.52e-05%	1,173,512

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.Arg24=
Coding: c.70A>C
MANE Select: NM_031308
dbSNP: rs74594612
Type: single nucleotide variant
Location: chr8:143873184 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)

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

Disease context

EPPK1-related disorder

Similar variants

EPPK1 p.Arg24Lys Likely benign ★ 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-arg24 (accessed [today's date]).

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