Is ESRP2 p.His529= (c.1587T>C) pathogenic?

ESRP2 p.His529= (c.1587T>C) is classified Likely benign in ESRP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-01-04). Ultra-rare (popmax 0.0165%, mid); Associated with ESRP2-related disorder.

What condition is associated with ESRP2 p.His529= (c.1587T>C)?

ESRP2 p.His529= (c.1587T>C) is associated with ESRP2-related disorder (ClinVar).

How common is ESRP2 p.His529= (c.1587T>C) in the general population?

ESRP2 p.His529= (c.1587T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

ESRP2 p.His529=

c.1587T>C · rs202161052 · VCV3054329

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

ESRP2-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 2.8	GERP -0.67, phastCons 1
Overall
CADD	7.643	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00892% 144/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.294%	340
Remaining individualsnot grpmax-eligible	0.0336%	2,976
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00549%	18,217
Admixed American	0.005%	20,007
European (non-Finnish)	0.00229%	43,704

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His529=
Coding: c.1587T>C
MANE Select: NM_024939
dbSNP: rs202161052
Type: single nucleotide variant
Location: chr16:68231302 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.87
Residue 529: the rrm 3 domain

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

Disease context

ESRP2-related disorder

Similar variants

ESRP2 p.His529Arg Uncertain significance ★ ⚠ same residue
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

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-his529 (accessed [today's date]).

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