Is EPS8L2 p.Ser339fs (c.1014del) pathogenic?

EPS8L2 p.Ser339fs (c.1014del) is classified Pathogenic in EPS8L2 (ClinVar, Single submitter, 2 submitters; last evaluated 2024-10-23). Absent from gnomAD; Associated with hearing loss, autosomal recessive 106.

What condition is associated with EPS8L2 p.Ser339fs (c.1014del)?

EPS8L2 p.Ser339fs (c.1014del) is associated with hearing loss, autosomal recessive 106 (ClinVar).

How common is EPS8L2 p.Ser339fs (c.1014del) in the general population?

EPS8L2 p.Ser339fs (c.1014del) is absent from gnomAD (gnomAD).

EPS8L2 p.Ser339fs

c.1014del · rs1554952443 · VCV433529

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 12 of 21
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: EPS8L2
Protein: p.Ser339fs
Coding: c.1014del
MANE Select: NM_022772
dbSNP: rs1554952443
Type: Deletion
Location: chr11:722117 (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.Lys333fs Pathogenic ★ same condition
EPS8L2 p.Pro471fs Likely pathogenic ★ same condition
EPS8L2 p.Ser339Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
EPS8L2 p.Val247fs Pathogenic same condition
EPS8L2 p.Asp473fs Pathogenic ★★ same condition
EPS8L2 p.Val478fs Pathogenic/Likely pathogenic ★★ same condition
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-ser339fs (accessed [today's date]).

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