EVC p.Pro551=
c.1653G>A · rs151293705 · VCV283123
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.297%, mid)
Conditions
2
acrofacial dysostosis, Weyers type
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 1.1 | GERP -2.9, phastCons 0.021 |
| Overall | ||
| CADD | 4.644 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.297%
Middle Eastern · 18/6,062 alleles
Filtering AF
0.192%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.159%
Overall
0.0125%
202/1,614,166 alleles · rare
exomes 132/1,461,890 · genomes 70/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.297% | 337 |
| African / African-American | 0.148% | 676 |
| South Asian | 0.0176% | 5,693 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,251 |
| Admixed American | 0.0133% | 7,503 |
| East Asian | 0.00446% | 22,442 |
| European (non-Finnish) | 0.00314% | 31,893 |
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
- EVC
- Protein
- p.Pro551=
- Coding
- c.1653G>A
- MANE Select
- NM_153717
- dbSNP
- rs151293705
- Type
- single nucleotide variant
- Location
- chr4:5783641 (GRCh38)
- Gene constraint
- LOEUF 1.134 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.49
Similar variants
- EVC p.Pro551Arg Uncertain significance ★★ ⚠ same residue
- EVC p.Pro551Leu Uncertain significance ★★ ⚠ same residue
- EVC p.Pro551fs Pathogenic ★ same residue
- EVC p.Pro551Ala Uncertain significance ★ ⚠ same residue
- EVC p.Pro551Ser Uncertain significance ★ ⚠ same residue
- EVC c.1098+1G>A Pathogenic/Likely pathogenic ★★ same condition
- EVC c.175-2A>G Pathogenic/Likely pathogenic ★★ same condition
- EVC c.1777-1G>A 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/evc-p-pro551 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown