LRIG2 p.Thr433=
c.1299T>C · rs148414072 · VCV709189
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.143%, 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 2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 9.697 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.143%
South Asian · 125/87,134 alleles
Filtering AF
0.123%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.115%
Overall
0.0542%
821/1,513,722 alleles · rare
exomes 775/1,361,370 · genomes 46/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.143% | 697 |
| European (non-Finnish) | 0.0586% | 1,706 |
| Remaining individualsnot grpmax-eligible | 0.039% | 2,562 |
| Admixed American | 0.0293% | 3,410 |
| Middle Eastern | 0.02% | 4,992 |
| African / African-American | 0.00957% | 10,449 |
| Finnishnot grpmax-eligible | 0.00956% | 10,455 |
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
- LRIG2
- Protein
- p.Thr433=
- Coding
- c.1299T>C
- MANE Select
- NM_014813
- dbSNP
- rs148414072
- Type
- single nucleotide variant
- Location
- chr1:113100474 (GRCh38)
- Gene constraint
- LOEUF 0.95 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 74.87
Similar variants
- LRIG2 p.Arg86Trp Uncertain significance ★★ ⚠ same type
- LRIG2 p.Glu11Ter Uncertain significance ★★ same type
- LRIG2 p.Lys245Arg Uncertain significance ★★ ⚠ same type
- LRIG2 c.2531-22G>A Benign ★★ same type
- LRIG2 p.Ala2= Likely benign ★★ same type
- LRIG2 p.Asp755Glu Benign ★★ same type
- LRIG2 p.Ile155Leu Likely benign ★★ same type
- LRIG2 p.Pro882Leu Likely benign ★★ 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/lrig2-p-thr433 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown