Is EPS8 p.Ala598Val (c.1793C>T) pathogenic?

EPS8 p.Ala598Val (c.1793C>T) is classified Uncertain significance in EPS8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-22). AlphaMissense: likely benign (0.09); Absent from gnomAD v4.1.

How common is EPS8 p.Ala598Val (c.1793C>T) in the general population?

EPS8 p.Ala598Val (c.1793C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPS8 p.Ala598Val (c.1793C>T)?

AlphaMissense predicts likely benign (score 0.09) — an in-silico prediction, not a clinical call.

EPS8 p.Ala598Val

c.1793C>T · rs2540277556 · VCV1717674

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.09 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.09	likely benign
REVEL	0.152	moderately benign-leaning
SaProt	LLR -6.05	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 6.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 62 kb · p 0.26 · regional, not allelic
Overall
CADD	22.3	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

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.Ala598Val
Coding: c.1793C>T
MANE Select: NM_004447
dbSNP: rs2540277556
Type: single nucleotide variant
Location: chr12:15640731 (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

Similar variants

EPS8 p.Ala598Thr Uncertain significance ★ ⚠ same residue
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-ala598val (accessed [today's date]).

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