Is SYN1 p.His272= (c.816C>T) pathogenic?

SYN1 p.His272= (c.816C>T) is classified Likely benign in SYN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-25). Ultra-rare (popmax 0.0107%, sas); Associated with epilepsy, X-linked 1, with variable learning disabilities and behavior disorders.

How common is SYN1 p.His272= (c.816C>T) in the general population?

SYN1 p.His272= (c.816C>T) is ultra-rare (popmax 0.0107%, sas) (gnomAD).

SYN1 p.His272=

Q: What condition is associated with SYN1 p.His272= (c.816C>T)?

SYN1 p.His272= (c.816C>T) 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.816C>T · rs763902035 · VCV436898

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0107%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.2
Overall
CADD	0.625	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0107% South Asian · 6/55,876 alleles

Filtering AF 0.00465% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00313%

Overall 0.000913% 11/1,205,392 alleles · ultra-rare exomes 10/1,094,327 · genomes 1/111,065 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0107%	9,313
East Asian	0.00298%	33,518
Finnishnot grpmax-eligible	0.00216%	46,232
African / African-American	0.00176%	56,746
European (non-Finnish)	0.000224%	446,592

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.His272=
Coding: c.816C>T
MANE Select: NM_006950
dbSNP: rs763902035
Type: single nucleotide variant
Location: chrX:47577460 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 272: the 'c; actin-binding and synaptic-vesicle binding' 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

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SYN1 p.Arg420Gln Likely pathogenic ★★ ⚠ same condition
SYN1 p.Arg422Ter Pathogenic ★★ same condition
SYN1 p.Gln483Ter Pathogenic ★★ same condition
SYN1 p.Gln555Ter Pathogenic ★★ same condition
SYN1 p.Glu121Ter Pathogenic/Likely 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-his272 (accessed [today's date]).

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