Is ESRP2 p.Pro596= (c.1788C>T) pathogenic?

ESRP2 p.Pro596= (c.1788C>T) is classified Likely benign in ESRP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-26). Rare (popmax 0.447%, nfe); Associated with ESRP2-related disorder.

What condition is associated with ESRP2 p.Pro596= (c.1788C>T)?

ESRP2 p.Pro596= (c.1788C>T) is associated with ESRP2-related disorder (ClinVar).

How common is ESRP2 p.Pro596= (c.1788C>T) in the general population?

ESRP2 p.Pro596= (c.1788C>T) is rare (popmax 0.447%, nfe) (gnomAD).

ESRP2 p.Pro596=

c.1788C>T · rs117260313 · VCV3038594

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.447%, nfe)

Conditions

ESRP2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.58	GERP -3.4, phastCons 0.99
Overall
CADD	5.338	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.447% European (non-Finnish) · 5,276/1,179,032 alleles

Filtering AF 0.437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.433%

Overall 0.359% 5,794/1,612,154 alleles · rare exomes 5,392/1,459,870 · genomes 402/152,284 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.447%	223
Remaining individualsnot grpmax-eligible	0.381%	262
Admixed American	0.214%	467
Finnishnot grpmax-eligible	0.141%	711
African / African-American	0.076%	1,315
Middle Eastern	0.0496%	2,016
South Asian	0.0022%	45,410

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: ESRP2
Protein: p.Pro596=
Coding: c.1788C>T
MANE Select: NM_024939
dbSNP: rs117260313
Type: single nucleotide variant
Location: chr16:68230951 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.87

Full ESRP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ESRP2-related disorder

Similar variants

ESRP2 p.Gly463Glu Uncertain significance ★★ ⚠ same condition
ESRP2 p.Leu681Phe Uncertain significance ★★ ⚠ same condition
ESRP2 p.Gly393Ser Uncertain significance ⚠ same condition
ESRP2 c.1299+7G>A Likely benign same condition
ESRP2 c.656-4T>C Benign same condition
ESRP2 c.711-9C>T Likely benign same condition
ESRP2 c.955-4A>G Likely benign same condition
ESRP2 p.Ala518Val 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/esrp2-p-pro596 (accessed [today's date]).

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