Is ESPN p.Arg32Cys (c.94C>T) pathogenic?

ESPN p.Arg32Cys (c.94C>T) is classified Uncertain significance in ESPN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-17). AlphaMissense: likely benign (0.1991); Very rare (popmax 0.00244%, amr); Associated with Inborn genetic diseases.

What condition is associated with ESPN p.Arg32Cys (c.94C>T)?

ESPN p.Arg32Cys (c.94C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ESPN p.Arg32Cys (c.94C>T) in the general population?

ESPN p.Arg32Cys (c.94C>T) is very rare (popmax 0.00244%, amr) (gnomAD).

What do computational predictors say about ESPN p.Arg32Cys (c.94C>T)?

AlphaMissense predicts likely benign (score 0.1991) — an in-silico prediction, not a clinical call.

ESPN p.Arg32Cys

c.94C>T · rs1461523328 · VCV2307883

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00244%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1991	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -10.86	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 3.8	GERP -2.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 21 kb · p 0.002 · regional, not allelic
Overall
CADD	25.1	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 0.00244% Admixed American · 1/40,950 alleles

Overall 0.000136% 2/1,469,184 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00244%	40,950
European (non-Finnish)	8.95e-05%	1,117,646

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.Arg32Cys
Coding: c.94C>T
MANE Select: NM_031475
dbSNP: rs1461523328
Type: single nucleotide variant
Location: chr1:6425049 (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.Arg32His 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
ESPN p.Arg335Cys Uncertain significance ★★ ⚠ same condition
ESPN p.Arg339Gln 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-arg32cys (accessed [today's date]).

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