Is EPPK1 p.Pro35Thr (c.103C>A) pathogenic?

EPPK1 p.Pro35Thr (c.103C>A) is classified Uncertain significance in EPPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-05). AlphaMissense: likely benign (0.0681); Absent from gnomAD v4.1; Associated with EPPK1-related disorder.

What condition is associated with EPPK1 p.Pro35Thr (c.103C>A)?

EPPK1 p.Pro35Thr (c.103C>A) is associated with EPPK1-related disorder (ClinVar).

How common is EPPK1 p.Pro35Thr (c.103C>A) in the general population?

EPPK1 p.Pro35Thr (c.103C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPPK1 p.Pro35Thr (c.103C>A)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

EPPK1 p.Pro35Thr

c.103C>A · rs77375433 · VCV2636784

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,589,870)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

EPPK1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.03	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.79	GERP -1.5
Regional constraint	o/e 1.18	unconstrained · MANE · 7,913 bp · p 8.9e-24 · regional, not allelic
Overall
CADD	0.643	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,589,870). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPPK1
Protein: p.Pro35Thr
Coding: c.103C>A
MANE Select: NM_031308
dbSNP: rs77375433
Type: single nucleotide variant
Location: chr8:143873151 (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.Gln2020Arg Uncertain significance ★ ⚠ same condition
EPPK1 p.Glu140Ter 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
EPPK1 p.Arg2356= Likely benign ★ same condition
EPPK1 p.Arg2364Gln 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-pro35thr (accessed [today's date]).

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