Is ESPN p.Asn717Ser (c.2150A>G) pathogenic?

ESPN p.Asn717Ser (c.2150A>G) is classified Uncertain significance in ESPN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2023-09-13). AlphaMissense: likely benign (0.0997); Ultra-rare (popmax 0.0332%, mid); Associated with Inborn genetic diseases.

What condition is associated with ESPN p.Asn717Ser (c.2150A>G)?

ESPN p.Asn717Ser (c.2150A>G) is associated with Inborn genetic diseases, sensorineural hearing loss disorder (ClinVar).

How common is ESPN p.Asn717Ser (c.2150A>G) in the general population?

ESPN p.Asn717Ser (c.2150A>G) is ultra-rare (popmax 0.0332%, mid) (gnomAD).

What do computational predictors say about ESPN p.Asn717Ser (c.2150A>G)?

AlphaMissense predicts likely benign (score 0.0997) — an in-silico prediction, not a clinical call.

ESPN p.Asn717Ser

c.2150A>G · rs921702586 · VCV523541

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0997 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0332%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0997	likely benign
REVEL	0.253	benign-leaning
SaProt	LLR -7.02	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 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.7 · regional, not allelic
Overall
CADD	23.0	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

Grpmax group 0.0332% Middle Eastern · 2/6,028 alleles

Filtering AF 0.00585% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.00248% 40/1,610,974 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0332%	3,014
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,526
South Asian	0.00332%	30,156
Remaining individualsnot grpmax-eligible	0.00321%	31,183
African / African-American	0.00267%	37,440
European (non-Finnish)	0.00254%	39,298

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.Asn717Ser
Coding: c.2150A>G
MANE Select: NM_031475
dbSNP: rs921702586
Type: single nucleotide variant
Location: chr1:6451921 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: sensorineural hearing loss disorder

Similar variants

ESPN p.Ala139Thr Uncertain significance ★★ ⚠ same condition
ESPN p.Ala23Thr Uncertain significance ★★ ⚠ same condition
ESPN p.Ala484Thr Uncertain significance ★★ ⚠ same condition
ESPN p.Ala729Glu Uncertain significance ★★ ⚠ same condition
ESPN p.Arg113His Uncertain significance ★★ ⚠ same condition
ESPN p.Arg335Cys Uncertain significance ★★ ⚠ same condition
ESPN p.Arg339Gln Uncertain significance ★★ ⚠ same condition
ESPN p.Arg478Cys 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-asn717ser (accessed [today's date]).

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