ESPNL p.Leu243=
c.729G>A · rs149388984 · VCV2652058
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.555%, 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 -0.82 | GERP -4.1, phastCons 0.001 |
| Overall | ||
| CADD | 5.516 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.555%
South Asian · 501/90,280 alleles
Filtering AF
0.515%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.499%
Overall
0.303%
4,871/1,609,138 alleles · rare
exomes 4,598/1,456,796 · genomes 273/152,342 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.555% | 180 |
| Middle Eastern | 0.43% | 233 |
| European (non-Finnish) | 0.343% | 291 |
| Remaining individualsnot grpmax-eligible | 0.255% | 392 |
| Ashkenazi Jewishnot grpmax-eligible | 0.129% | 775 |
| Admixed American | 0.0639% | 1,565 |
| African / African-American | 0.0574% | 1,743 |
| Finnishnot grpmax-eligible | 0.0351% | 2,853 |
| East Asian | 0.00447% | 22,359 |
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
- ESPNL
- Protein
- p.Leu243=
- Coding
- c.729G>A
- MANE Select
- NM_194312
- dbSNP
- rs149388984
- Type
- single nucleotide variant
- Location
- chr2:238107847 (GRCh38)
- Gene constraint
- LOEUF 1.651 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.57
Similar variants
- ESPNL p.Arg167Gln Benign ★★ same type
- ESPNL p.Arg351Cys Benign ★★ same type
- ESPNL c.672+1G>A Uncertain significance ★ same type
- ESPNL p.Ala112Ser Uncertain significance ★ ⚠ same type
- ESPNL p.Ala144Asp Uncertain significance ★ ⚠ same type
- ESPNL p.Ala144Thr Uncertain significance ★ ⚠ same type
- ESPNL p.Ala145Thr Uncertain significance ★ ⚠ same type
- ESPNL p.Ala159Thr 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/espnl-p-leu243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown