Is ESPN p.Ser824fs (c.2470_2473del) pathogenic?

ESPN p.Ser824fs (c.24702473del) is classified Pathogenic in ESPN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2004-08-01). Very rare (popmax 0.0011%, sas); Associated with autosomal recessive nonsyndromic hearing loss 36.

What condition is associated with ESPN p.Ser824fs (c.2470_2473del)?

ESPN p.Ser824fs (c.2470_2473del) is associated with autosomal recessive nonsyndromic hearing loss 36 (ClinVar).

How common is ESPN p.Ser824fs (c.2470_2473del) in the general population?

ESPN p.Ser824fs (c.2470_2473del) is very rare (popmax 0.0011%, sas) (gnomAD).

ESPN p.Ser824fs

c.2470_2473del · rs1569770998 · VCV4418

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

autosomal recessive nonsyndromic hearing loss 36

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (13 of 13) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.8	GERP -1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,078 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000274% 4/1,461,188 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,078
European (non-Finnish)	0.000254%	393,337

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ESPN
Protein: p.Ser824fs
Coding: c.2470_2473del
MANE Select: NM_031475
dbSNP: rs1569770998
Type: Deletion
Location: chr1:6460048 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 824: the 'disordered' region

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

Disease context

autosomal recessive nonsyndromic hearing loss 36 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ESPN p.Arg550fs Pathogenic ★ same condition
ESPN p.Lys666fs Pathogenic ★ same condition
ESPN p.Ser694fs Pathogenic ★ same condition
ESPN p.Pro431fs Uncertain significance ★ same condition
ESPN p.Gly831_Tyr832insTer Pathogenic/Likely pathogenic same condition
ESPN p.Lys663fs Pathogenic same condition
ESPN c.1464+1G>A Likely pathogenic ★★ same condition
ESPN c.2339_2341del 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/espn-p-ser824fs (accessed [today's date]).

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