Is EPPK1 p.Pro10Arg (c.29C>G) pathogenic?

EPPK1 p.Pro10Arg (c.29C>G) is classified Uncertain significance in EPPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.0858); Very rare (popmax 0.00273%, afr).

How common is EPPK1 p.Pro10Arg (c.29C>G) in the general population?

EPPK1 p.Pro10Arg (c.29C>G) is very rare (popmax 0.00273%, afr) (gnomAD).

What do computational predictors say about EPPK1 p.Pro10Arg (c.29C>G)?

AlphaMissense predicts likely benign (score 0.0858) — an in-silico prediction, not a clinical call.

EPPK1 p.Pro10Arg

c.29C>G · VCV3845577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0858 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00273%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0858	likely benign
REVEL	0.012	strongly benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -0.6, phastCons 0.32
Regional constraint	o/e 1.18	unconstrained · MANE · 7,913 bp · p 8.9e-24 · regional, not allelic
Overall
CADD	11.81	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00273% African / African-American · 2/73,340 alleles

Filtering AF 0.000453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000169%

Overall 0.00019% 3/1,575,156 alleles · very rare exomes 1/1,422,952 · genomes 2/152,204 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00273%	36,670
European (non-Finnish)	8.57e-05%	1,166,216

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.Pro10Arg
Coding: c.29C>G
MANE Select: NM_031308
Type: single nucleotide variant
Location: chr8:143873225 (GRCh38)
Gene constraint: LOEUF 1.929 · pLI 0.12 (gnomAD)
Residue 10: the 'disordered' 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-pro10arg (accessed [today's date]).

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