Is SYN1 p.Lys142= (c.426A>G) pathogenic?

SYN1 p.Lys142= (c.426A>G) is classified Benign/Likely benign in SYN1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Rare (popmax 0.92%, sas); Associated with History of neurodevelopmental disorder.

What condition is associated with SYN1 p.Lys142= (c.426A>G)?

SYN1 p.Lys142= (c.426A>G) is associated with History of neurodevelopmental disorder, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

How common is SYN1 p.Lys142= (c.426A>G) in the general population?

SYN1 p.Lys142= (c.426A>G) is rare (popmax 0.92%, sas) (gnomAD).

SYN1 p.Lys142=

c.426A>G · rs145911562 · VCV207459

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.92%, sas)

Conditions

History of neurodevelopmental disorder

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 4.9	GERP 2.3, phastCons 1
Overall
CADD	13.64	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.92% South Asian · 523/56,826 alleles

Filtering AF 0.855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.829%

Overall 0.113% 1,363/1,209,945 alleles · rare exomes 1,288/1,097,866 · genomes 75/112,079 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.92%	109
Middle Eastern	0.46%	218
Remaining individualsnot grpmax-eligible	0.155%	643
European (non-Finnish)	0.0773%	1,293
Finnishnot grpmax-eligible	0.0644%	1,553
Ashkenazi Jewishnot grpmax-eligible	0.0454%	2,203
Admixed American	0.0153%	6,536
African / African-American	0.00873%	11,454
East Asian	0.00592%	16,883

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.Lys142=
Coding: c.426A>G
MANE Select: NM_006950
dbSNP: rs145911562
Type: single nucleotide variant
Location: chrX:47607150 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 142: 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

History of neurodevelopmental disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

SYN1 p.Lys142Ile 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
SYN1 p.Gln555Ter 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-lys142 (accessed [today's date]).

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