Is ESPN p.Gly263Asp (c.788G>A) pathogenic?

ESPN p.Gly263Asp (c.788G>A) is classified Uncertain significance in ESPN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-27). AlphaMissense: ambiguous (0.5246); Very rare (popmax 0.00189%, amr); Associated with Inborn genetic diseases.

What condition is associated with ESPN p.Gly263Asp (c.788G>A)?

ESPN p.Gly263Asp (c.788G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ESPN p.Gly263Asp (c.788G>A) in the general population?

ESPN p.Gly263Asp (c.788G>A) is very rare (popmax 0.00189%, amr) (gnomAD).

What do computational predictors say about ESPN p.Gly263Asp (c.788G>A)?

AlphaMissense predicts ambiguous (score 0.5246) — an in-silico prediction, not a clinical call.

ESPN p.Gly263Asp

c.788G>A · VCV4618802

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5246 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00189%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5246	ambiguous
REVEL	0.513	indeterminate
SaProt	LLR -10.45	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 21 kb · p 0.002 · regional, not allelic
Overall
CADD	29.7	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00189% Admixed American · 1/52,944 alleles

Overall 0.000144% 2/1,393,056 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00189%	52,944
South Asian	0.0012%	83,668

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.Gly263Asp
Coding: c.788G>A
MANE Select: NM_031475
Type: single nucleotide variant
Location: chr1:6440738 (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

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-gly263asp (accessed [today's date]).

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