Is SRPX2 p.Arg161= (c.481C>A) pathogenic?

SRPX2 p.Arg161= (c.481C>A) is classified Benign/Likely benign in SRPX2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-09). Rare (popmax 0.224%, nfe); Associated with rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked.

What condition is associated with SRPX2 p.Arg161= (c.481C>A)?

SRPX2 p.Arg161= (c.481C>A) is associated with rolandic epilepsy, intellectual disability, and speech dyspraxia, X-linked (ClinVar).

How common is SRPX2 p.Arg161= (c.481C>A) in the general population?

SRPX2 p.Arg161= (c.481C>A) is rare (popmax 0.224%, 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.Arg161=

c.481C>A · rs150552508 · VCV207371

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.224%, 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 2.9	GERP -0.22, phastCons 1
Overall
CADD	10.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.224% European (non-Finnish) · 2,003/895,086 alleles

Filtering AF 0.216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.212%

Overall 0.174% 2,100/1,209,407 alleles · rare exomes 1,989/1,097,174 · genomes 111/112,233 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.224%	447
Remaining individualsnot grpmax-eligible	0.143%	700
Finnishnot grpmax-eligible	0.0365%	2,739
African / African-American	0.0157%	6,366
Ashkenazi Jewishnot grpmax-eligible	0.00454%	22,021
Admixed American	0.00437%	22,903

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.Arg161=
Coding: c.481C>A
MANE Select: NM_014467
dbSNP: rs150552508
Type: single nucleotide variant
Location: chrX:100664899 (GRCh38)
Structure: AlphaFold pLDDT 86.75
Residue 161: the sushi 2 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 p.Arg161Gln Uncertain significance ★ same residue
SRPX2 p.Arg161Pro Uncertain significance ★ ⚠ same residue
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

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-arg161 (accessed [today's date]).

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