Is ESPN p.Asp588Asn (c.1762G>A) pathogenic?

ESPN p.Asp588Asn (c.1762G>A) is classified Uncertain significance in ESPN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-26). AlphaMissense: likely benign (0.1076); Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 36.

What condition is associated with ESPN p.Asp588Asn (c.1762G>A)?

ESPN p.Asp588Asn (c.1762G>A) is associated with autosomal recessive nonsyndromic hearing loss 36 (ClinVar).

How common is ESPN p.Asp588Asn (c.1762G>A) in the general population?

ESPN p.Asp588Asn (c.1762G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ESPN p.Asp588Asn (c.1762G>A)?

AlphaMissense predicts likely benign (score 0.1076) — an in-silico prediction, not a clinical call.

ESPN p.Asp588Asn

c.1762G>A · rs2522885327 · VCV3065194

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1076 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,399,336)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 36

Computational evidence

Protein change
AlphaMissense	0.1076	likely benign
REVEL	0.235	benign-leaning
SaProt	LLR -7.49	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7	GERP 1.4, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.7 · regional, not allelic
Overall
CADD	23.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,399,336). 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.Asp588Asn
Coding: c.1762G>A
MANE Select: NM_031475
dbSNP: rs2522885327
Type: single nucleotide variant
Location: chr1:6448938 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 588: 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-asp588asn (accessed [today's date]).

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