LCT p.Cys322=
c.966T>C · rs781555422 · VCV1583161
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0418%, sas)
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 3.4 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 15.59 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0418%
South Asian · 38/90,916 alleles
Filtering AF
0.0313%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0276%
Overall
0.0103%
165/1,605,212 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0418% | 2,393 |
| Middle Eastern | 0.0166% | 6,040 |
| Remaining individualsnot grpmax-eligible | 0.0161% | 6,220 |
| European (non-Finnish) | 0.00939% | 10,653 |
| African / African-American | 0.00534% | 18,718 |
| Admixed American | 0.00333% | 30,010 |
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.Cys322=
- Coding
- c.966T>C
- MANE Select
- NM_002299
- dbSNP
- rs781555422
- Type
- single nucleotide variant
- Location
- chr2:135822040 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 86.63
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-cys322 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown