LCT p.Arg222=
c.664C>A · rs147426095 · VCV2061222
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0145%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>A here scores Δ0.28 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -1.5, phastCons 0.009 |
| Overall | ||
| CADD | 3.453 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0145%
European (non-Finnish) · 171/1,179,944 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.012%
Overall
0.0108%
175/1,613,778 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0145% | 6,900 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,233 |
| African / African-American | 0.00267% | 37,429 |
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
- LCT
- Protein
- p.Arg222=
- Coding
- c.664C>A
- MANE Select
- NM_002299
- dbSNP
- rs147426095
- Type
- single nucleotide variant
- Location
- chr2:135833167 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
- Residue 222
- the 'glycosyl hydrolase-1 1; region i' region
Similar variants
- LCT p.Arg222Ter Pathogenic ★ same residue
- LCT p.Arg222Gln Uncertain significance ★ ⚠ same residue
- LCT c.4866+2T>G Likely pathogenic ★★ same type
- LCT p.Gln1179Ter Pathogenic/Likely pathogenic ★★ same type
- LCT p.Lys787Ter Pathogenic/Likely pathogenic ★★ same type
- LCT p.Tyr1390Ter Pathogenic ★★ same type
- LCT c.4173+5G>A Uncertain significance ★★ same type
- LCT p.Ala1398Glu 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/lct-p-arg222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown