Is SYN1 p.Thr48= (c.144C>G) pathogenic?

SYN1 p.Thr48= (c.144C>G) is classified Benign in SYN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). Very rare (popmax 0.00179%, afr); Associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders.

How common is SYN1 p.Thr48= (c.144C>G) in the general population?

SYN1 p.Thr48= (c.144C>G) is very rare (popmax 0.00179%, afr) (gnomAD).

SYN1 p.Thr48=

Q: What condition is associated with SYN1 p.Thr48= (c.144C>G)?

SYN1 p.Thr48= (c.144C>G) is associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

Q: How is X-linked epilepsy-learning disabilities-behavior disorders syndrome inherited?

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

c.144C>G · rs1363812576 · VCV2792784

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00179%, afr)

Conditions

epilepsy, X-linked 1, with variable learning disabilities and behavior disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.023	GERP -3.8, phastCons 0.26
Overall
CADD	4.421	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00179% African / African-American · 1/55,777 alleles

Overall 8.6e-05% 1/1,163,326 alleles · very rare exomes 1/1,049,590 · genomes 0/113,736 · 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: SYN1
Protein: p.Thr48=
Coding: c.144C>G
MANE Select: NM_006950
dbSNP: rs1363812576
Type: single nucleotide variant
Location: chrX:47619585 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 48: the 'disordered' region; the 'b; linker' region

Full SYN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

epilepsy, X-linked 1, with variable learning disabilities and behavior disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked epilepsy-learning disabilities-behavior disorders syndrome (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood

Similar variants

SYN1 p.Thr48Ile Uncertain significance ★★ ⚠ same residue
SYN1 p.Thr48Ser Uncertain significance ★ ⚠ same residue
SYN1 c.528-2A>T Pathogenic/Likely pathogenic ★★ same condition
SYN1 c.838-2A>G Likely pathogenic ★★ same condition
SYN1 p.Arg234Ter Pathogenic ★★ same condition
SYN1 p.Arg420Gln Likely pathogenic ★★ ⚠ same condition
SYN1 p.Arg422Ter Pathogenic ★★ same condition
SYN1 p.Gln483Ter Pathogenic ★★ 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/syn1-p-thr48 (accessed [today's date]).

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