Is EPS8L2 p.Ser455Phe (c.1364C>T) pathogenic?

EPS8L2 p.Ser455Phe (c.1364C>T) is classified Uncertain significance in EPS8L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-22). AlphaMissense: likely benign (0.1256); Absent from gnomAD v4.1.

How common is EPS8L2 p.Ser455Phe (c.1364C>T) in the general population?

EPS8L2 p.Ser455Phe (c.1364C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about EPS8L2 p.Ser455Phe (c.1364C>T)?

AlphaMissense predicts likely benign (score 0.1256) — an in-silico prediction, not a clinical call.

EPS8L2 p.Ser455Phe

c.1364C>T · rs2494648058 · VCV2098606

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1256 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1256	likely benign
REVEL	0.113	moderately benign-leaning
SaProt	LLR -8.69	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 6.9	GERP 0.99, phastCons 0.99
Regional constraint	o/e 1.19	unconstrained · MANE · 18 kb · p 2.2e-09 · regional, not allelic
Overall
CADD	18.56	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: EPS8L2
Protein: p.Ser455Phe
Coding: c.1364C>T
MANE Select: NM_022772
dbSNP: rs2494648058
Type: single nucleotide variant
Location: chr11:723263 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 2 PDB
Residue 455: the 'disordered' region

Full EPS8L2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

EPS8L2 p.Glu165Ter Likely pathogenic ★★ same type
EPS8L2 p.Arg102Trp Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg193Gln Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg245Gln Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg272Trp Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg365Cys Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg506Leu Uncertain significance ★★ ⚠ same type
EPS8L2 p.Arg76Trp 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/eps8l2-p-ser455phe (accessed [today's date]).

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