MEGF8 p.Pro2571=
c.7713G>A · rs200748447 · VCV703258
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0828%, mid)
Conditions
1
MEGF8-related Carpenter syndrome
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 -6.2 | |
| Overall | ||
| CADD | 0.74 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0828%
Middle Eastern · 5/6,040 alleles
Filtering AF
0.0326%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0224%
Overall
0.0076%
122/1,605,856 alleles · ultra-rare
exomes 112/1,453,572 · genomes 10/152,284 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0828% | 1,208 |
| South Asian | 0.0354% | 2,823 |
| Remaining individualsnot grpmax-eligible | 0.0257% | 3,888 |
| East Asian | 0.0112% | 8,953 |
| Admixed American | 0.00839% | 11,925 |
| European (non-Finnish) | 0.00484% | 20,647 |
| African / African-American | 0.00267% | 37,489 |
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
- MEGF8
- Protein
- p.Pro2571=
- Coding
- c.7713G>A
- MANE Select
- NM_001271938
- dbSNP
- rs200748447
- Type
- single nucleotide variant
- Location
- chr19:42375950 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI <0.01 (gnomAD)
Similar variants
- MEGF8 p.Arg419Ter Pathogenic/Likely pathogenic ★★ same condition
- MEGF8 p.Arg991Ter Pathogenic/Likely pathogenic ★★ same condition
- MEGF8 p.Ala1472Val Uncertain significance ★★ ⚠ same condition
- MEGF8 p.Ala1572Thr Uncertain significance ★★ ⚠ same condition
- MEGF8 p.Ala176Gly Uncertain significance ★★ ⚠ same condition
- MEGF8 p.Ala1791Ser Uncertain significance ★★ same condition
- MEGF8 p.Ala2104Ser Uncertain significance ★★ ⚠ same condition
- MEGF8 p.Ala2349Gly Uncertain significance ★★ 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/megf8-p-pro2571 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown