ESCO2 p.Val170=
c.510G>A · rs112031297 · VCV257054
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.19%, afr)
Conditions
1
Roberts-SC phocomelia syndrome
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 -0.24 | GERP -3.5 |
| Overall | ||
| CADD | 0.263 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.19%
African / African-American · 2,394/75,032 alleles
Filtering AF
3.08%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.04%
Overall
0.178%
2,872/1,614,102 alleles · low-frequency
exomes 1,428/1,461,812 · genomes 1,444/152,290 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.19% | 31 |
| Remaining individualsnot grpmax-eligible | 0.256% | 391 |
| Admixed American | 0.242% | 414 |
| Middle Eastern | 0.214% | 466 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0878% | 1,139 |
| European (non-Finnish) | 0.0108% | 9,219 |
| South Asian | 0.00659% | 15,179 |
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
- ESCO2
- Protein
- p.Val170=
- Coding
- c.510G>A
- MANE Select
- NM_001017420
- dbSNP
- rs112031297
- Type
- single nucleotide variant
- Location
- chr8:27776818 (GRCh38)
- Gene constraint
- LOEUF 1.013 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 58.81
Similar variants
- ESCO2 p.Val170Gly Uncertain significance ⚠ same residue
- ESCO2 c.1013+1G>A Likely pathogenic ★★ same condition
- ESCO2 c.1131+1G>A Pathogenic ★★ same condition
- ESCO2 c.1131+1G>T Pathogenic ★★ same condition
- ESCO2 c.1132-7A>G Pathogenic/Likely pathogenic ★★ same condition
- ESCO2 c.1353+1G>T Likely pathogenic ★★ same condition
- ESCO2 p.Arg169Ter Pathogenic ★★ same condition
- ESCO2 p.Arg552Ter Pathogenic/Likely pathogenic ★★ same condition
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/esco2-p-val170 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown