SYNGAP1 p.Phe645=
c.1935T>C · rs145406441 · VCV416780
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.203%, afr)
Conditions
2
Inborn genetic diseases
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 0.29 | GERP -4.3, phastCons 1 |
| Overall | ||
| CADD | 5.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.203%
African / African-American · 152/74,976 alleles
Filtering AF
0.176%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.166%
Overall
0.0103%
166/1,613,952 alleles · rare
exomes 85/1,461,810 · genomes 81/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.203% | 493 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0203% | 4,934 |
| Admixed American | 0.00667% | 15,003 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,834 |
| European (non-Finnish) | 8.47e-05% | 1,179,993 |
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
- SYNGAP1
- Protein
- p.Phe645=
- Coding
- c.1935T>C
- MANE Select
- NM_006772
- dbSNP
- rs145406441
- Type
- single nucleotide variant
- Location
- chr6:33441194 (GRCh38)
- Gene constraint
- LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 60.43
- Residue 645
- the ras-gap domain; a UniProt-annotated variant site (in mrd5; uncertain significance); a UniProt-annotated variant site (in mrd5)
Similar variants
- SYNGAP1 c.1532-1G>A Pathogenic/Likely pathogenic ★★ same condition
- SYNGAP1 c.1676+1G>A Pathogenic/Likely pathogenic ★★ same condition
- SYNGAP1 c.2294+1G>T Pathogenic ★★ same condition
- SYNGAP1 c.3583-1G>A Likely pathogenic ★★ same condition
- SYNGAP1 c.3583-6G>A Pathogenic/Likely pathogenic ★★ same condition
- SYNGAP1 c.3583-9G>A Pathogenic ★★ same condition
- SYNGAP1 c.509+1G>A Pathogenic ★★ same condition
- SYNGAP1 c.509+1G>T 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/syngap1-p-phe645 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown