Is ESPN p.Arg782Trp (c.2344C>T) pathogenic?

ESPN p.Arg782Trp (c.2344C>T) is classified Uncertain significance in ESPN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-17). AlphaMissense: likely benign (0.1024); Ultra-rare (popmax 0.0134%, eas); Associated with Inborn genetic diseases.

What condition is associated with ESPN p.Arg782Trp (c.2344C>T)?

ESPN p.Arg782Trp (c.2344C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ESPN p.Arg782Trp (c.2344C>T) in the general population?

ESPN p.Arg782Trp (c.2344C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about ESPN p.Arg782Trp (c.2344C>T)?

AlphaMissense predicts likely benign (score 0.1024) — an in-silico prediction, not a clinical call.

ESPN p.Arg782Trp

c.2344C>T · rs201586165 · VCV2510835

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1024 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1024	likely benign
REVEL	0.203	benign-leaning
SaProt	LLR -14.92	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.23	GERP -3, phastCons 0.01
Regional constraint	o/e 0.98	unconstrained · MANE · 11 kb · p 0.7 · regional, not allelic
Overall
CADD	21.5	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 0.0134% East Asian · 6/44,622 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00396%

Overall 0.00218% 35/1,607,332 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,437
Admixed American	0.00341%	29,333
South Asian	0.00221%	45,166
European (non-Finnish)	0.00195%	51,164
Remaining individualsnot grpmax-eligible	0.00161%	62,220
African / African-American	0.00133%	74,928

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.Arg782Trp
Coding: c.2344C>T
MANE Select: NM_031475
dbSNP: rs201586165
Type: single nucleotide variant
Location: chr1:6457202 (GRCh38)
Gene constraint: LOEUF 1.307 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.76
Residue 782: the 'disordered' region

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.Arg782Pro Uncertain significance ★★ ⚠ same residue
ESPN p.Arg782Gln Uncertain significance ★★ ⚠ same residue
ESPN p.Arg782Leu Uncertain significance ★ ⚠ same residue
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

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-arg782trp (accessed [today's date]).

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