SPEF2 p.Val816=
c.2448A>G · VCV4681836
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
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 1.7 | GERP -2.4, phastCons 0.018 |
| Overall | ||
| CADD | 1.827 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,360 alleles
Overall
6.2e-05%
1/1,613,092 alleles · very rare
exomes 1/1,460,842 · genomes 0/152,250 · joint denominator
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.Val816=
- Coding
- c.2448A>G
- MANE Select
- NM_024867
- Type
- single nucleotide variant
- Location
- chr5:35704603 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.30
- Residue 816
- a UniProt-annotated variant site (in spgf43; loss of protein expression; changed sperm axoneme assembly); a UniProt-annotated variant site (found in a female patient with primary ciliary dyskinesia-like symptoms including chronic sinusitis, bronchitis, chronic wet cough and recurrent pneumonia; uncertain significance)
Similar variants
- 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
- SPEF2 c.2141+130C>T 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-val816 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown