SPEF2 p.Val1771=
c.5313C>T · rs1365001146 · VCV2655404
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0164%, mid)
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 0.63 | GERP 2.5, phastCons 0.99 |
| Overall | ||
| CADD | 7.47 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0164%
Middle Eastern · 1/6,082 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.00161%
26/1,613,808 alleles · ultra-rare
exomes 25/1,461,706 · genomes 1/152,102 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0164% | 6,082 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,241 |
| South Asian | 0.0022% | 45,512 |
| European (non-Finnish) | 0.00178% | 56,190 |
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.Val1771=
- Coding
- c.5313C>T
- MANE Select
- NM_024867
- dbSNP
- rs1365001146
- Type
- single nucleotide variant
- Location
- chr5:35807187 (GRCh38)
- Gene constraint
- LOEUF 0.923 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 71.30
- Residue 1771
- 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); a UniProt-annotated variant site (found in 2 brothers with severe asthenozoospermia and a primary ciliary dyskinesia-like phenotype with recurrent airway infections, bronchiectasis, rhinosinusitis and otitis media; likely pathogenic)
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-val1771 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown