Is SYN1 p.Asn170= (c.510T>C) pathogenic?

SYN1 p.Asn170= (c.510T>C) is classified Benign in SYN1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). Common (popmax 42.1%, afr) — too common for a highly-penetrant pathogenic allele; Associated with intellectual disability, X-linked 50.

What condition is associated with SYN1 p.Asn170= (c.510T>C)?

SYN1 p.Asn170= (c.510T>C) is associated with intellectual disability, X-linked 50, epilepsy, X-linked 1, with variable learning disabilities and behavior disorders (ClinVar).

SYN1 p.Asn170=

Q: How common is SYN1 p.Asn170= (c.510T>C) in the general population?

SYN1 p.Asn170= (c.510T>C) is common (popmax 42.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.510T>C · rs1142636 · VCV96364

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Common

common (popmax 42.1%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

intellectual disability, X-linked 50

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 0.15	GERP -4.1, phastCons 0.12
Overall
CADD	2.003	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.1% African / African-American · 23,601/56,034 alleles

Filtering AF 41.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 41.5%

Overall 37.8% 455,142/1,205,344 alleles · common exomes 412,886/1,096,885 · genomes 42,256/108,459 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	42.1%	2
Admixed American	39.6%	3
Ashkenazi Jewishnot grpmax-eligible	39.4%	3
Amishnot grpmax-eligible	39.2%	3
Finnishnot grpmax-eligible	38.6%	3
European (non-Finnish)	38.3%	3
Remaining individualsnot grpmax-eligible	38.1%	3
Middle Eastern	36.7%	3
South Asian	31.9%	3
East Asian	20.8%	5

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.Asn170=
Coding: c.510T>C
MANE Select: NM_006950
dbSNP: rs1142636
Type: single nucleotide variant
Location: chrX:47606962 (GRCh38)
Structure: AlphaFold pLDDT 69.86
Residue 170: 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

intellectual disability, X-linked 50 — 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.Asn170Tyr 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.Gln249Ter Pathogenic/Likely 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-asn170 (accessed [today's date]).

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