Is ESPN p.Ala586fs (c.1756dup) pathogenic?

ESPN p.Ala586fs (c.1756dup) is classified Pathogenic in ESPN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2008-12-01). Absent from gnomAD; Associated with Deafness, autosomal recessive 36, without vestibular involvement.

What condition is associated with ESPN p.Ala586fs (c.1756dup)?

ESPN p.Ala586fs (c.1756dup) is associated with Deafness, autosomal recessive 36, without vestibular involvement (ClinVar).

How common is ESPN p.Ala586fs (c.1756dup) in the general population?

ESPN p.Ala586fs (c.1756dup) is absent from gnomAD (gnomAD).

ESPN p.Ala586fs

c.1756dup · rs1569712066 · VCV4424

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Deafness, autosomal recessive 36, without vestibular involvement

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 8 of 13
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP 0.26, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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: ESPN
Protein: p.Ala586fs
Coding: c.1756dup
MANE Select: NM_031475
dbSNP: rs1569712066
Type: Duplication
Location: chr1:6448931 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 586: the 'disordered' region

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

Disease context

Deafness, autosomal recessive 36, without vestibular involvement — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ESPN p.His82fs Likely pathogenic ★ same type
ESPN p.Ser568fs Likely pathogenic ★ same type
ESPN p.Trp258Ter Likely pathogenic ★ same type
ESPN c.2053_2061+20dup Conflicting classifications of pathogenicity ★ same type
ESPN p.Asp518fs Uncertain significance ★ same type
ESPN p.Pro567_Ser568insPro Uncertain significance ★ same type
ESPN c.295-147dup Likely benign ★ same type
ESPN c.489-236dup Benign ★ 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/espn-p-ala586fs (accessed [today's date]).

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