Is SRPX2 p.Cys306= (c.918T>C) pathogenic?

SRPX2 p.Cys306= (c.918T>C) is classified Benign in SRPX2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-06-12). Rare (popmax 0.312%, afr); Associated with rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked.

What condition is associated with SRPX2 p.Cys306= (c.918T>C)?

SRPX2 p.Cys306= (c.918T>C) is associated with rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (ClinVar).

How common is SRPX2 p.Cys306= (c.918T>C) in the general population?

SRPX2 p.Cys306= (c.918T>C) is rare (popmax 0.312%, afr) (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.Cys306=

c.918T>C · rs34728871 · VCV696905

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.312%, afr)

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 0.81	GERP -2.2, phastCons 1
Overall
CADD	10.18	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.312% African / African-American · 179/57,352 alleles

Filtering AF 0.275% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.26%

Overall 0.016% 194/1,209,398 alleles · rare exomes 110/1,097,016 · genomes 84/112,382 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.312%	320
Remaining individualsnot grpmax-eligible	0.021%	4,751
Admixed American	0.00655%	15,278
European (non-Finnish)	0.000223%	447,531

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.Cys306=
Coding: c.918T>C
MANE Select: NM_014467
dbSNP: rs34728871
Type: single nucleotide variant
Location: chrX:100666890 (GRCh38)
Structure: AlphaFold pLDDT 86.75
Residue 306: a disulfide bond; the sushi 3 domain

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-cys306 (accessed [today's date]).

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