Is EPPK1 p.Pro1229= (c.3687C>T) pathogenic?

EPPK1 p.Pro1229= (c.3687C>T) is classified Likely benign in EPPK1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-03-01). Rare (popmax 0.379%, nfe).

How common is EPPK1 p.Pro1229= (c.3687C>T) in the general population?

EPPK1 p.Pro1229= (c.3687C>T) is rare (popmax 0.379%, nfe) (gnomAD).

EPPK1 p.Pro1229=

c.3687C>T · rs144925578 · VCV2658935

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.379%, nfe)

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 -11	GERP -3.1
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.379% European (non-Finnish) · 4,370/1,153,688 alleles

Filtering AF 0.369% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.366%

Overall 0.307% 4,792/1,559,000 alleles · rare exomes 4,446/1,406,650 · genomes 346/152,350 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.768%	130
European (non-Finnish)grpmax	0.379%	264
Remaining individualsnot grpmax-eligible	0.265%	377
Admixed American	0.229%	436
Finnishnot grpmax-eligible	0.106%	941
African / African-American	0.0827%	1,208
East Asian	0.0211%	4,733
Ashkenazi Jewishnot grpmax-eligible	0.0143%	7,012
South Asian	0.00116%	86,034

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro1229=
Coding: c.3687C>T
MANE Select: NM_031308
dbSNP: rs144925578
Type: single nucleotide variant
Location: chr8:143869567 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)

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

Similar variants

EPPK1 p.Pro1229His Uncertain significance ★ ⚠ same residue
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

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-pro1229 (accessed [today's date]).

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