Is ESRP2 p.Arg43= (c.129G>A) pathogenic?

ESRP2 p.Arg43= (c.129G>A) is classified Benign in ESRP2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Rare (popmax 0.611%, nfe); Associated with ESRP2-related disorder.

What condition is associated with ESRP2 p.Arg43= (c.129G>A)?

ESRP2 p.Arg43= (c.129G>A) is associated with ESRP2-related disorder (ClinVar).

How common is ESRP2 p.Arg43= (c.129G>A) in the general population?

ESRP2 p.Arg43= (c.129G>A) is rare (popmax 0.611%, nfe) (gnomAD).

ESRP2 p.Arg43=

c.129G>A · rs150603076 · VCV3033371

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.611%, nfe)

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 -1	GERP -5.1, phastCons 0.001
Overall
CADD	6.954	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.611% European (non-Finnish) · 7,201/1,177,918 alleles

Filtering AF 0.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.595%

Overall 0.578% 9,300/1,607,668 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.84%	54
Amishnot grpmax-eligible	1.76%	57
European (non-Finnish)grpmax	0.611%	164
Remaining individualsnot grpmax-eligible	0.505%	198
South Asian	0.395%	253
Ashkenazi Jewishnot grpmax-eligible	0.278%	360
Middle Eastern	0.264%	378
Admixed American	0.173%	578
African / African-American	0.104%	961

Finnish 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.Arg43=
Coding: c.129G>A
MANE Select: NM_024939
dbSNP: rs150603076
Type: single nucleotide variant
Location: chr16:68235917 (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-arg43 (accessed [today's date]).

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