Is ESPN p.Pro430= (c.1290C>G) pathogenic?

ESPN p.Pro430= (c.1290C>G) is classified Likely benign in ESPN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-07). Absent from gnomAD v4.1; Associated with ESPN-related disorder.

What condition is associated with ESPN p.Pro430= (c.1290C>G)?

ESPN p.Pro430= (c.1290C>G) is associated with ESPN-related disorder (ClinVar).

How common is ESPN p.Pro430= (c.1290C>G) in the general population?

ESPN p.Pro430= (c.1290C>G) is absent from gnomAD v4.1 (gnomAD).

ESPN p.Pro430=

c.1290C>G · rs776899743 · VCV3041506

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,530,376)

Conditions

ESPN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.7	GERP -2.5
Overall
CADD	0.159	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,530,376). 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.Pro430=
Coding: c.1290C>G
MANE Select: NM_031475
dbSNP: rs776899743
Type: single nucleotide variant
Location: chr1:6445761 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 430: the 'disordered' region

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

Disease context

ESPN-related disorder

Similar variants

ESPN p.Pro430Thr Uncertain significance ★ ⚠ same residue
ESPN c.1464+1G>T Likely pathogenic ★ same condition
ESPN c.2062-1G>T Likely pathogenic ★ same condition
ESPN c.991-2A>G Likely pathogenic ★ same condition
ESPN p.Gln447Ter Likely pathogenic ★ same condition
ESPN p.Ser719Arg Likely pathogenic ★ same condition
ESPN c.*4C>T Likely benign same condition
ESPN p.Arg791= Likely benign 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-pro430 (accessed [today's date]).

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