Is EPPK1 p.Ala987Ser (c.2959G>T) pathogenic?

EPPK1 p.Ala987Ser (c.2959G>T) is classified Uncertain significance in EPPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely benign (0.3296); Very rare (popmax 0.000171%, nfe).

How common is EPPK1 p.Ala987Ser (c.2959G>T) in the general population?

EPPK1 p.Ala987Ser (c.2959G>T) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about EPPK1 p.Ala987Ser (c.2959G>T)?

AlphaMissense predicts likely benign (score 0.3296) — an in-silico prediction, not a clinical call.

EPPK1 p.Ala987Ser

c.2959G>T · rs375057041 · VCV2543995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3296 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.3296	likely benign
REVEL	0.653	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 7,913 bp · p 8.9e-24 · regional, not allelic
Overall
CADD	23.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,170,096 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00014% 2/1,429,762 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.Ala987Ser
Coding: c.2959G>T
MANE Select: NM_031308
dbSNP: rs375057041
Type: single nucleotide variant
Location: chr8:143870295 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 987: the 'interaction with krt5' region

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

Similar variants

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
EPPK1 p.Ala1205Thr 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-ala987ser (accessed [today's date]).

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