Is EPS8 p.Arg764Ser (c.2292G>T) pathogenic?

EPS8 p.Arg764Ser (c.2292G>T) is classified Uncertain significance in EPS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely pathogenic (0.839); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with EPS8 p.Arg764Ser (c.2292G>T)?

EPS8 p.Arg764Ser (c.2292G>T) is associated with Inborn genetic diseases (ClinVar).

How common is EPS8 p.Arg764Ser (c.2292G>T) in the general population?

EPS8 p.Arg764Ser (c.2292G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPS8 p.Arg764Ser (c.2292G>T)?

AlphaMissense predicts likely pathogenic (score 0.839) — an in-silico prediction, not a clinical call.

EPS8 p.Arg764Ser

c.2292G>T · rs2540202538 · VCV2603960

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.839 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.839	likely pathogenic
REVEL	0.158	moderately benign-leaning
SaProt	LLR -9.13	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.63	GERP -1.2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.26 · regional, not allelic
Overall
CADD	19.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: EPS8
Protein: p.Arg764Ser
Coding: c.2292G>T
MANE Select: NM_004447
dbSNP: rs2540202538
Type: single nucleotide variant
Location: chr12:15623221 (GRCh38)
Gene constraint: LOEUF 0.443 · pLI 1.00 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.77 · 2 PDB
Residue 764: the 'helix bundle 3' region; an α-helix; the 'effector region' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPS8 p.Ala150Val Uncertain significance ★★ ⚠ same condition
EPS8 p.Ala416Asp Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg195Trp Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg403Trp Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg432Gln Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg434Cys Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg597Cys Uncertain significance ★★ ⚠ same condition
EPS8 p.Arg597Ser Uncertain significance ★★ ⚠ same condition

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-arg764ser (accessed [today's date]).

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