MEGF8 p.Phe197=
c.591C>T · VCV4704451
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00801%, afr)
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 1.1 | phastCons 1 |
| Overall | ||
| CADD | 8.537 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00801%
African / African-American · 6/74,920 alleles
Filtering AF
0.00347%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00229%
Overall
0.000372%
6/1,613,596 alleles · very rare
exomes 4/1,461,400 · genomes 2/152,196 · joint denominator
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.Phe197=
- Coding
- c.591C>T
- MANE Select
- NM_001271938
- Type
- single nucleotide variant
- Location
- chr19:42335067 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI <0.01 (gnomAD)
- Residue 197
- the egf-like 2 domain
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-phe197 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown