Is EPS8L2 p.Ile321fs (c.961dup) pathogenic?

EPS8L2 p.Ile321fs (c.961dup) is classified Pathogenic in EPS8L2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-09). Associated with hearing loss, autosomal recessive 106.

What condition is associated with EPS8L2 p.Ile321fs (c.961dup)?

EPS8L2 p.Ile321fs (c.961dup) is associated with hearing loss, autosomal recessive 106 (ClinVar).

EPS8L2 p.Ile321fs

c.961dup · VCV3601081

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hearing loss, autosomal recessive 106

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.7	GERP -2.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: EPS8L2
Protein: p.Ile321fs
Coding: c.961dup
MANE Select: NM_022772
Type: Duplication
Location: chr11:721964 (GRCh38)
Gene constraint: LOEUF 1.164 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.67 · 2 PDB

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

Disease context

hearing loss, autosomal recessive 106 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EPS8L2 p.Asp473fs Pathogenic ★★ same condition
EPS8L2 p.Val478fs Pathogenic/Likely pathogenic ★★ same condition
EPS8L2 p.Ala279fs Pathogenic ★ same condition
EPS8L2 p.Gln121fs Likely pathogenic ★ same condition
EPS8L2 p.Leu440fs Likely pathogenic ★ same condition
EPS8L2 p.Ile321Val Conflicting classifications of pathogenicity ★ ⚠ same residue
EPS8L2 p.Met27Thr Uncertain significance ★★ ⚠ same condition
EPS8L2 p.Thr69Met 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/eps8l2-p-ile321fs (accessed [today's date]).

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