LCT p.Ala424=
c.1272G>A · rs534576693 · VCV2185185
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00933%, afr)
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 -15 | GERP -3.7 |
| Overall | ||
| CADD | 0.053 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00933%
African / African-American · 7/75,046 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00308%
Overall
0.00173%
28/1,613,982 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00933% | 10,721 |
| East Asian | 0.00446% | 22,434 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| Admixed American | 0.00167% | 60,024 |
| European (non-Finnish) | 0.00136% | 73,752 |
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.Ala424=
- Coding
- c.1272G>A
- MANE Select
- NM_002299
- dbSNP
- rs534576693
- Type
- single nucleotide variant
- Location
- chr2:135817776 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
- Residue 424
- the 'glycosyl hydrolase-1 2; region ii' region
Similar variants
- LCT p.Ala424Val Uncertain significance ★★ ⚠ same residue
- LCT p.Ala424Glu 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-ala424 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown