ESCO2 p.Ala256=
c.768G>A · rs372611248 · VCV1099813
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 1.3 | GERP -0.38, phastCons 0.77 |
| Overall | ||
| CADD | 4.838 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,014 alleles
Filtering AF
0.00729%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00554%
Overall
0.00187%
30/1,605,144 alleles · ultra-rare
exomes 17/1,452,884 · genomes 13/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,014 |
| African / African-American | 0.0135% | 7,424 |
| East Asian | 0.00223% | 44,850 |
| Remaining individualsnot grpmax-eligible | 0.00161% | 62,080 |
| European (non-Finnish) | 0.00144% | 69,296 |
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.Ala256=
- Coding
- c.768G>A
- MANE Select
- NM_001017420
- dbSNP
- rs372611248
- Type
- single nucleotide variant
- Location
- chr8:27777076 (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.Ala256Gly Uncertain significance ★ ⚠ same residue
- ESCO2 p.Ala256Val 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
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-ala256 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown