Is EEPD1 p.Ser342Leu (c.1025C>T) pathogenic?

EEPD1 p.Ser342Leu (c.1025C>T) is classified Uncertain significance in EEPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-18). AlphaMissense: likely benign (0.0842); Ultra-rare (popmax 0.0223%, eas).

How common is EEPD1 p.Ser342Leu (c.1025C>T) in the general population?

EEPD1 p.Ser342Leu (c.1025C>T) is ultra-rare (popmax 0.0223%, eas) (gnomAD).

What do computational predictors say about EEPD1 p.Ser342Leu (c.1025C>T)?

AlphaMissense predicts likely benign (score 0.0842) — an in-silico prediction, not a clinical call.

EEPD1 p.Ser342Leu

c.1025C>T · VCV3843530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0842 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0223%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0842	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -7.27	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 2.6, phastCons 0.69
Regional constraint	o/e 0.90	unconstrained · MANE · 145 kb · p 0.0078 · regional, not allelic
Overall
CADD	19.08	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 0.0223% East Asian · 10/44,866 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00294% 43/1,461,824 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0223%	4,487
Admixed American	0.00333%	30,014
European (non-Finnish)	0.00254%	39,333
Remaining individualsnot grpmax-eligible	0.0016%	62,502

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.Ser342Leu
Coding: c.1025C>T
MANE Select: NM_030636
Type: single nucleotide variant
Location: chr7:36281209 (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.Ser342Pro 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-ser342leu (accessed [today's date]).

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