Is ESRP2 p.Pro10Ser (c.28C>T) pathogenic?

ESRP2 p.Pro10Ser (c.28C>T) is classified Uncertain significance in ESRP2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.092); Ultra-rare (popmax 0.0236%, amr).

How common is ESRP2 p.Pro10Ser (c.28C>T) in the general population?

ESRP2 p.Pro10Ser (c.28C>T) is ultra-rare (popmax 0.0236%, amr) (gnomAD).

What do computational predictors say about ESRP2 p.Pro10Ser (c.28C>T)?

AlphaMissense predicts likely benign (score 0.092) — an in-silico prediction, not a clinical call.

ESRP2 p.Pro10Ser

c.28C>T · rs770884448 · VCV3090563

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.092 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0236%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.092	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.83	GERP -1.2, phastCons 0.23
Regional constraint	o/e 0.89	unconstrained · MANE · 5,816 bp · p 0.00093 · regional, not allelic
Overall
CADD	17.84	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0236% Admixed American · 9/38,204 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00917%

Overall 0.00114% 17/1,489,242 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0236%	4,245
Middle Eastern	0.0196%	5,114
East Asian	0.00262%	38,128
Remaining individualsnot grpmax-eligible	0.00174%	57,412
European (non-Finnish)	0.000443%	225,675

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.Pro10Ser
Coding: c.28C>T
MANE Select: NM_024939
dbSNP: rs770884448
Type: single nucleotide variant
Location: chr16:68236018 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.87
Residue 10: the 'disordered' region

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

Similar variants

ESRP2 p.Gly122Arg Uncertain significance ★★ ⚠ same type
ESRP2 p.Gly463Glu Uncertain significance ★★ ⚠ same type
ESRP2 p.Leu681Phe Uncertain significance ★★ ⚠ same type
ESRP2 p.Ala691Thr Benign ★★ same type
ESRP2 p.Thr475= Benign ★★ same type
ESRP2 p.Ala20Pro Uncertain significance ★ ⚠ same type
ESRP2 p.Ala273Val Uncertain significance ★ ⚠ same type
ESRP2 p.Ala322Thr Uncertain significance ★ ⚠ same type

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-pro10ser (accessed [today's date]).

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