Is EPPK1 p.Ala98Val (c.293C>T) pathogenic?

EPPK1 p.Ala98Val (c.293C>T) is classified Uncertain significance in EPPK1 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-06-28). AlphaMissense: ambiguous (0.528); Rare (popmax 0.223%, afr).

How common is EPPK1 p.Ala98Val (c.293C>T) in the general population?

EPPK1 p.Ala98Val (c.293C>T) is rare (popmax 0.223%, afr) (gnomAD).

What do computational predictors say about EPPK1 p.Ala98Val (c.293C>T)?

AlphaMissense predicts ambiguous (score 0.528) — an in-silico prediction, not a clinical call.

EPPK1 p.Ala98Val

c.293C>T · rs201067978 · VCV2213970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.528 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.223%, afr)

Computational evidence

Protein change
AlphaMissense	0.528	ambiguous
REVEL	0.726	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	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	22.7	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 0.223% African / African-American · 166/74,570 alleles

Filtering AF 0.195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.0123% 197/1,604,224 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.223%	449
Remaining individualsnot grpmax-eligible	0.0258%	3,870
Middle Eastern	0.0165%	6,048
Admixed American	0.0119%	8,419
South Asian	0.00111%	90,488
European (non-Finnish)	0.000511%	195,793

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.Ala98Val
Coding: c.293C>T
MANE Select: NM_031308
dbSNP: rs201067978
Type: single nucleotide variant
Location: chr8:143872961 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 98: 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-ala98val (accessed [today's date]).

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