Is EEPD1 p.Ala352Glu (c.1055C>A) pathogenic?

EEPD1 p.Ala352Glu (c.1055C>A) is classified Uncertain significance in EEPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: ambiguous (0.3687); Very rare (popmax 0.0067%, nfe).

How common is EEPD1 p.Ala352Glu (c.1055C>A) in the general population?

EEPD1 p.Ala352Glu (c.1055C>A) is very rare (popmax 0.0067%, nfe) (gnomAD).

What do computational predictors say about EEPD1 p.Ala352Glu (c.1055C>A)?

AlphaMissense predicts ambiguous (score 0.3687) — an in-silico prediction, not a clinical call.

EEPD1 p.Ala352Glu

c.1055C>A · VCV4246836

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3687 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0067%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3687	ambiguous
REVEL	0.475	indeterminate
SaProt	LLR -9.12	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.18	GERP 0.32
Regional constraint	o/e 0.90	unconstrained · MANE · 145 kb · p 0.0078 · regional, not allelic
Overall
CADD	14.2	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 0.0067% European (non-Finnish) · 79/1,179,164 alleles

Filtering AF 0.00547% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.00527% 85/1,612,096 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0067%	14,926
African / African-American	0.00401%	24,907
Remaining individualsnot grpmax-eligible	0.0032%	31,204
Admixed American	0.00167%	59,836

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.Ala352Glu
Coding: c.1055C>A
MANE Select: NM_030636
Type: single nucleotide variant
Location: chr7:36284699 (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.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
EEPD1 p.Ala358Val 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-ala352glu (accessed [today's date]).

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