SPEF2 p.Gln99=
c.297A>G · rs78762910 · VCV722366
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.15%, afr)
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 -0.97 | GERP -3.5 |
| Overall | ||
| CADD | 3.694 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.15%
African / African-American · 2,365/75,014 alleles
Filtering AF
3.05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3%
Overall
0.162%
2,613/1,613,818 alleles · low-frequency
exomes 1,234/1,461,556 · genomes 1,379/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.15% | 32 |
| Remaining individualsnot grpmax-eligible | 0.221% | 453 |
| Admixed American | 0.13% | 769 |
| Middle Eastern | 0.0495% | 2,020 |
| South Asian | 0.0198% | 5,059 |
| European (non-Finnish) | 0.000932% | 107,256 |
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
- SPEF2
- Protein
- p.Gln99=
- Coding
- c.297A>G
- MANE Select
- NM_024867
- dbSNP
- rs78762910
- Type
- single nucleotide variant
- Location
- chr5:35641566 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.30
- Residue 99
- the calponin-homology (ch) domain
Similar variants
- SPEF2 p.Gln99Arg Uncertain significance ★ ⚠ same residue
- SPEF2 p.Asp797Gly Uncertain significance ★★ ⚠ same type
- SPEF2 p.Glu116Lys Uncertain significance ★★ ⚠ same type
- SPEF2 p.Glu1752Gln Uncertain significance ★★ ⚠ same type
- SPEF2 c.1167+46T>C Benign ★★ same type
- SPEF2 c.1168-85A>G Benign ★★ same type
- SPEF2 c.1525-111C>G Benign ★★ same type
- SPEF2 c.2037+17A>C Benign ★★ 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/spef2-p-gln99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown