LCT p.Ala523=
c.1569G>A · rs376254978 · VCV1626547
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0493%, mid)
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 -13 | GERP -3.9 |
| Overall | ||
| CADD | 0.732 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0493%
Middle Eastern · 3/6,084 alleles
Filtering AF
0.0134%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00715%
Overall
0.00149%
24/1,614,044 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0493% | 2,028 |
| Admixed American | 0.00833% | 12,000 |
| African / African-American | 0.00801% | 12,488 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,829 |
| East Asian | 0.00223% | 44,874 |
| South Asian | 0.0022% | 45,540 |
| European (non-Finnish) | 0.000339% | 295,011 |
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.Ala523=
- Coding
- c.1569G>A
- MANE Select
- NM_002299
- dbSNP
- rs376254978
- Type
- single nucleotide variant
- Location
- chr2:135817479 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
- Residue 523
- the 'glycosyl hydrolase-1 2; region ii' region
Similar variants
- 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
- LCT p.Ala1483Thr Uncertain significance ★★ ⚠ same type
- LCT p.Ala148Gly 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-ala523 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown