RAPGEF4 p.Ser705=
c.2115C>T · rs150552209 · VCV717581
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.18%, sas)
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 -7.3 | GERP -3.7 |
| Overall | ||
| CADD | 0.304 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.18%
South Asian · 1,989/91,056 alleles
Filtering AF
2.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.07%
Overall
0.19%
3,073/1,613,974 alleles · low-frequency
exomes 2,693/1,461,868 · genomes 380/152,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.18% | 46 |
| Ashkenazi Jewishnot grpmax-eligible | 0.703% | 142 |
| African / African-American | 0.519% | 193 |
| Remaining individualsnot grpmax-eligible | 0.317% | 316 |
| Middle Eastern | 0.247% | 404 |
| Admixed American | 0.065% | 1,538 |
| East Asian | 0.0401% | 2,492 |
| European (non-Finnish) | 0.0182% | 5,488 |
| Finnishnot grpmax-eligible | 0.00312% | 32,008 |
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
- RAPGEF4
- Protein
- p.Ser705=
- Coding
- c.2115C>T
- MANE Select
- NM_007023
- dbSNP
- rs150552209
- Type
- single nucleotide variant
- Location
- chr2:173018762 (GRCh38)
- Gene constraint
- LOEUF 0.542 · pLI 0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.41
Similar variants
- RAPGEF4 p.Gly706Arg Likely benign ★★ same type
- RAPGEF4 p.Ile516Val Benign ★★ same type
- RAPGEF4 p.Pro548= Benign ★★ same type
- RAPGEF4 p.Thr231= Benign ★★ same type
- RAPGEF4 p.Ala125Thr Uncertain significance ★ ⚠ same type
- RAPGEF4 p.Ala13Val Uncertain significance ★ ⚠ same type
- RAPGEF4 p.Ala17Ser Uncertain significance ★ ⚠ same type
- RAPGEF4 p.Ala213Thr Uncertain significance ★ ⚠ same type
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/rapgef4-p-ser705 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown