GIT1 p.Leu516=
c.1548G>C · rs144464404 · VCV3039162
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0515%, nfe)
Conditions
1
GIT1-related 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 0.15 | GERP -3.5, phastCons 0.95 |
| Overall | ||
| CADD | 6.353 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0515%
European (non-Finnish) · 607/1,179,434 alleles
Filtering AF
0.0481%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0467%
Overall
0.041%
661/1,612,178 alleles · ultra-rare
exomes 618/1,459,974 · genomes 43/152,204 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0515% | 1,943 |
| Remaining individualsnot grpmax-eligible | 0.0368% | 2,714 |
| Admixed American | 0.0167% | 5,998 |
| Middle Eastern | 0.0164% | 6,082 |
| African / African-American | 0.016% | 6,244 |
| Finnishnot grpmax-eligible | 0.0111% | 8,991 |
| South Asian | 0.0011% | 91,060 |
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
- GIT1
- Protein
- p.Leu516=
- Coding
- c.1548G>C
- MANE Select
- NM_014030
- dbSNP
- rs144464404
- Type
- single nucleotide variant
- Location
- chr17:29576283 (GRCh38)
- Gene constraint
- LOEUF 0.257 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.72
- Residue 516
- the 'interaction with nck2 and grin3a' region; the 'required for localization at synapses' region; the 'interaction with ikbkg' region
Disease context
GIT1-related disorder
Similar variants
- GIT1 c.2010-4G>A Likely benign same condition
- GIT1 p.Ala515= Likely benign same condition
- GIT1 p.Arg717= Likely benign same condition
- GIT1 p.Asp418= Likely benign same condition
- GIT1 p.Gln250= Likely benign same condition
- GIT1 p.Glu221= Likely benign same condition
- GIT1 p.Glu622= Likely benign same condition
- GIT1 p.His50= Likely benign 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/git1-p-leu516 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown