Is ESPN p.Glu816Ter (c.2446G>T) pathogenic?

ESPN p.Glu816Ter (c.2446G>T) is classified Likely pathogenic in ESPN (ClinVar, Single submitter, 1 submitter; last evaluated 2018-09-19). Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 36.

What condition is associated with ESPN p.Glu816Ter (c.2446G>T)?

ESPN p.Glu816Ter (c.2446G>T) is associated with autosomal recessive nonsyndromic hearing loss 36 (ClinVar).

How common is ESPN p.Glu816Ter (c.2446G>T) in the general population?

ESPN p.Glu816Ter (c.2446G>T) is absent from gnomAD v4.1 (gnomAD).

ESPN p.Glu816Ter

c.2446G>T · rs1485674839 · VCV623132

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	nonsense (stop-gain)	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
REVEL	0.135	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.04, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: ESPN
Protein: p.Glu816Ter
Coding: c.2446G>T
MANE Select: NM_031475
dbSNP: rs1485674839
Type: single nucleotide variant
Location: chr1:6460027 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 816: 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 c.1464+1G>A Likely pathogenic ★★ same condition
ESPN p.Ala624Thr Uncertain significance ★★ ⚠ same condition
ESPN p.Arg755Cys Uncertain significance ★★ ⚠ same condition
ESPN p.Asp744Asn Uncertain significance ★★ ⚠ same condition
ESPN p.Gly747Ser Uncertain significance ★★ ⚠ same condition
ESPN p.Lys476Gln Uncertain significance ★★ ⚠ same condition
ESPN p.Ser312Leu Uncertain significance ★★ ⚠ same condition
ESPN p.Ser362Leu 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-glu816ter (accessed [today's date]).

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