Is EPS8 p.Leu377= (c.1131A>G) pathogenic?

EPS8 p.Leu377= (c.1131A>G) is classified Likely benign in EPS8 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-29). Absent from gnomAD v4.1; Associated with EPS8-related disorder.

What condition is associated with EPS8 p.Leu377= (c.1131A>G)?

EPS8 p.Leu377= (c.1131A>G) is associated with EPS8-related disorder (ClinVar).

How common is EPS8 p.Leu377= (c.1131A>G) in the general population?

EPS8 p.Leu377= (c.1131A>G) is absent from gnomAD v4.1 (gnomAD).

EPS8 p.Leu377=

c.1131A>G · rs2540355251 · VCV3052351

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,612,662)

Conditions

EPS8-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.47	GERP -2.5, phastCons 0.086
Overall
CADD	6.475	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,612,662). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EPS8
Protein: p.Leu377=
Coding: c.1131A>G
MANE Select: NM_004447
dbSNP: rs2540355251
Type: single nucleotide variant
Location: chr12:15654264 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB

Full EPS8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

EPS8-related disorder

Similar variants

EPS8 p.Pro210= Likely benign same condition
EPS8 c.205-8A>G Uncertain significance ★★ same type
EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same type
EPS8 p.Ala219Val Uncertain significance ★★ ⚠ same type
EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same type
EPS8 p.Arg432Gln 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/eps8-p-leu377 (accessed [today's date]).

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