Is SRPX2 p.Pro437= (c.1311C>T) pathogenic?

SRPX2 p.Pro437= (c.1311C>T) is classified Likely benign in SRPX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-08-25). Very rare (popmax 0.000112%, nfe); Associated with rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked.

What condition is associated with SRPX2 p.Pro437= (c.1311C>T)?

SRPX2 p.Pro437= (c.1311C>T) is associated with rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (ClinVar).

How common is SRPX2 p.Pro437= (c.1311C>T) in the general population?

SRPX2 p.Pro437= (c.1311C>T) is very rare (popmax 0.000112%, nfe) (gnomAD).

How is Rolandic epilepsy-speech dyspraxia syndrome inherited?

Typically Autosomal dominant, X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

SRPX2 p.Pro437=

c.1311C>T · rs2083222587 · VCV1118300

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked

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 -12	GERP -3.4
Overall
CADD	0.126	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/895,399 alleles

Overall 8.26e-05% 1/1,211,339 alleles · very rare exomes 1/1,098,156 · genomes 0/113,183 · joint denominator

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: SRPX2
Protein: p.Pro437=
Coding: c.1311C>T
MANE Select: NM_014467
dbSNP: rs2083222587
Type: single nucleotide variant
Location: chrX:100670900 (GRCh38)
Structure: AlphaFold pLDDT 86.75

Full SRPX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Rolandic epilepsy-speech dyspraxia syndrome (Orphanet):

Inheritance: Autosomal dominant, X-linked dominant
Onset: Antenatal, Infancy, Neonatal

Similar variants

SRPX2 c.961+1G>A Uncertain significance ★★ same condition
SRPX2 p.Ala201Val Uncertain significance ★★ ⚠ same condition
SRPX2 p.Arg185Cys Uncertain significance ★★ ⚠ same condition
SRPX2 p.Arg185Leu Uncertain significance ★★ ⚠ same condition
SRPX2 p.Arg413His Uncertain significance ★★ ⚠ same condition
SRPX2 p.Arg430His Uncertain significance ★★ ⚠ same condition
SRPX2 p.Arg54Gln Uncertain significance ★★ ⚠ same condition
SRPX2 p.Asn327Lys 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/srpx2-p-pro437 (accessed [today's date]).

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