Is EEPD1 p.Ser63Asn (c.188G>A) pathogenic?

EEPD1 p.Ser63Asn (c.188G>A) is classified Uncertain significance in EEPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-26). AlphaMissense: likely benign (0.1514); Very rare (popmax 0.0011%, sas).

How common is EEPD1 p.Ser63Asn (c.188G>A) in the general population?

EEPD1 p.Ser63Asn (c.188G>A) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about EEPD1 p.Ser63Asn (c.188G>A)?

AlphaMissense predicts likely benign (score 0.1514) — an in-silico prediction, not a clinical call.

EEPD1 p.Ser63Asn

c.188G>A · VCV3506820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1514 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1514	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 145 kb · p 0.0078 · regional, not allelic
Overall
CADD	21.3	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

Grpmax group 0.0011% South Asian · 1/91,090 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000434% 7/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,090
European (non-Finnish)	0.000508%	196,675

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.Ser63Asn
Coding: c.188G>A
MANE Select: NM_030636
Type: single nucleotide variant
Location: chr7:36154512 (GRCh38)
Gene constraint: LOEUF 0.561 · pLI 0.81 (gnomAD)
Structure: AlphaFold pLDDT 74.72 · 3 PDB
Residue 63: the hhh domain

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.Ala352Glu 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-ser63asn (accessed [today's date]).

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