Is EEPD1 p.Pro318Ala (c.952C>G) pathogenic?

EEPD1 p.Pro318Ala (c.952C>G) is classified Uncertain significance in EEPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-14). AlphaMissense: likely benign (0.1338); Very rare (popmax 0.000169%, nfe).

How common is EEPD1 p.Pro318Ala (c.952C>G) in the general population?

EEPD1 p.Pro318Ala (c.952C>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about EEPD1 p.Pro318Ala (c.952C>G)?

AlphaMissense predicts likely benign (score 0.1338) — an in-silico prediction, not a clinical call.

EEPD1 p.Pro318Ala

c.952C>G · rs1456148227 · VCV3087395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1338	likely benign
REVEL	0.684	pathogenic-leaning
SaProt	LLR -9.70	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.6, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 145 kb · p 0.0078 · regional, not allelic
Overall
CADD	22.9	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 0.000169% European (non-Finnish) · 2/1,180,044 alleles

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

Overall 0.000124% 2/1,614,026 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: EEPD1
Protein: p.Pro318Ala
Coding: c.952C>G
MANE Select: NM_030636
dbSNP: rs1456148227
Type: single nucleotide variant
Location: chr7:36281136 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 3 PDB

Full EEPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EEPD1 p.Pro318Leu Uncertain significance ★ ⚠ same residue
EEPD1 p.Ala107Gly Uncertain significance ★ ⚠ same type
EEPD1 p.Ala120Gly Uncertain significance ★ ⚠ same type
EEPD1 p.Ala130Val Uncertain significance ★ ⚠ same type
EEPD1 p.Ala186Pro Uncertain significance ★ ⚠ same type
EEPD1 p.Ala186Thr Uncertain significance ★ ⚠ same type
EEPD1 p.Ala215Thr Uncertain significance ★ ⚠ same type
EEPD1 p.Ala349Val 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/eepd1-p-pro318ala (accessed [today's date]).

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