Is EPPK1 p.Ala1772= (c.5316C>T) pathogenic?

EPPK1 p.Ala1772= (c.5316C>T) is classified Likely benign in EPPK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-16). Ultra-rare (popmax 0.0533%, afr); Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Ala1772= (c.5316C>T)?

EPPK1 p.Ala1772= (c.5316C>T) is associated with EPPK1-related disorder (ClinVar).

How common is EPPK1 p.Ala1772= (c.5316C>T) in the general population?

EPPK1 p.Ala1772= (c.5316C>T) is ultra-rare (popmax 0.0533%, afr) (gnomAD).

EPPK1 p.Ala1772=

c.5316C>T · rs111341821 · VCV3036036

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0533%, 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 1.3	GERP 0.46, phastCons 0.034
Overall
CADD	6.111	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0533% African / African-American · 40/75,040 alleles

Filtering AF 0.0401% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0356%

Overall 0.00459% 74/1,613,648 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0533%	1,876
Remaining individualsnot grpmax-eligible	0.0416%	2,403
Middle Eastern	0.0165%	6,062
Admixed American	0.00666%	15,006
European (non-Finnish)	0.000254%	393,298

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.Ala1772=
Coding: c.5316C>T
MANE Select: NM_031308
dbSNP: rs111341821
Type: single nucleotide variant
Location: chr8:143867938 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 1772: 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.Ala1772Ser Uncertain significance ★ ⚠ 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-ala1772 (accessed [today's date]).

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