LRAT p.Ser175=
c.525T>C · rs104893848 · VCV1078570
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0103%, nfe)
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 0.84 | phastCons 1 |
| Overall | ||
| CADD | 10.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0103%
European (non-Finnish) · 122/1,179,954 alleles
Filtering AF
0.00884%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00828%
Overall
0.00806%
130/1,613,154 alleles · ultra-rare
exomes 115/1,461,278 · genomes 15/151,876 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0103% | 9,672 |
| Remaining individualsnot grpmax-eligible | 0.008% | 12,494 |
| African / African-American | 0.00401% | 24,943 |
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
- LRAT
- Protein
- p.Ser175=
- Coding
- c.525T>C
- MANE Select
- NM_004744
- dbSNP
- rs104893848
- Type
- single nucleotide variant
- Location
- chr4:154744851 (GRCh38)
- Gene constraint
- LOEUF 1.214 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 83.69
- Residue 175
- the lrat domain; a UniProt-annotated variant site (in lca14; loss of function)
Similar variants
- LRAT p.Ser175Arg Pathogenic ★ same residue
- LRAT p.Arg47Ter Pathogenic/Likely pathogenic ★★ same type
- LRAT p.Arg55Gly Pathogenic/Likely pathogenic ★★ same type
- LRAT p.Arg55Trp Pathogenic ★★ same type
- LRAT p.Cys168Ter Pathogenic ★★ same type
- LRAT p.Leu157Pro Likely pathogenic ★★ same type
- LRAT c.*2625A>G Uncertain significance ★★ same type
- LRAT p.Ala120Gly 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/lrat-p-ser175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown