LCT p.His712=
c.2136C>T · rs574860581 · VCV2900715
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 -3.4 | GERP -3.6 |
| Overall | ||
| CADD | 0.454 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,016 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000867%
14/1,614,202 alleles · very rare
exomes 12/1,461,874 · genomes 2/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,005 |
| East Asian | 0.00223% | 44,886 |
| South Asian | 0.0022% | 45,542 |
| Finnishnot grpmax-eligible | 0.00156% | 64,032 |
| European (non-Finnish) | 0.000593% | 168,576 |
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.His712=
- Coding
- c.2136C>T
- MANE Select
- NM_002299
- dbSNP
- rs574860581
- Type
- single nucleotide variant
- Location
- chr2:135812528 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
- Residue 712
- the 'glycosyl hydrolase-1 2; region ii' region
Similar variants
- LCT p.His712Tyr 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
- LCT p.Ala1483Thr 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-his712 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown