ME2 p.Val468=
c.1404T>A · rs142847061 · VCV94060
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.75%, eas)
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 -7.8 | GERP -4.4 |
| Overall | ||
| CADD | 0.134 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.75%
East Asian · 2,127/44,808 alleles
Filtering AF
4.58%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.51%
Overall
0.286%
4,606/1,611,994 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 4.75% | 21 |
| Admixed American | 2.8% | 36 |
| Remaining individualsnot grpmax-eligible | 0.7% | 143 |
| South Asian | 0.124% | 804 |
| Middle Eastern | 0.066% | 1,514 |
| African / African-American | 0.0653% | 1,531 |
| Finnishnot grpmax-eligible | 0.0422% | 2,369 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0237% | 4,225 |
| European (non-Finnish) | 0.014% | 7,142 |
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
- ME2
- Protein
- p.Val468=
- Coding
- c.1404T>A
- MANE Select
- NM_001378328 · reported on NM_002396
- dbSNP
- rs142847061
- Type
- single nucleotide variant
- Location
- chr18:50932347 (GRCh38)
- Residue 468
- a UniProt-annotated variant site (in lmphm9); the cadherin 3 domain
Similar variants
- CELSR1 p.Ala2442Val Uncertain significance ★★ ⚠ same type
- CELSR1 p.Ala2955Thr Uncertain significance ★★ ⚠ same type
- CELSR1 p.Ala396Ser Uncertain significance ★★ ⚠ same type
- CELSR1 p.Ala617Ser Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1323Gln Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1379His Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same type
- CELSR1 p.Arg1720Trp Uncertain significance ★★ ⚠ same type
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/me2-p-val468 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown