SEM1 p.Glu61=
c.183G>A · rs144707454 · VCV738972
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0527%, 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 1.8 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 8.664 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0527%
European (non-Finnish) · 611/1,160,134 alleles
Filtering AF
0.0492%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0478%
Overall
0.0403%
641/1,590,756 alleles · ultra-rare
exomes 603/1,438,716 · genomes 38/152,040 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0527% | 1,899 |
| Remaining individualsnot grpmax-eligible | 0.0243% | 4,109 |
| Admixed American | 0.0101% | 9,938 |
| Finnishnot grpmax-eligible | 0.0094% | 10,636 |
| African / African-American | 0.00403% | 24,831 |
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
- SEM1
- Protein
- p.Glu61=
- Coding
- c.183G>A
- MANE Select
- NM_006304
- dbSNP
- rs144707454
- Type
- single nucleotide variant
- Location
- chr7:96688954 (GRCh38)
- Gene constraint
- LOEUF 0.754 · pLI 0.77 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 69.87 · 140 PDB
- Residue 61
- an α-helix
Similar variants
- ECD p.Asn61Ser Uncertain significance ★ ⚠ same residue
- ECD p.Ala121Gly Uncertain significance ★ same type
- ECD p.Ala122Ser Uncertain significance ★ ⚠ same type
- ECD p.Ala150Thr Uncertain significance ★ ⚠ same type
- ECD p.Ala234Ser Uncertain significance ★ ⚠ same type
- ECD p.Ala329Val Uncertain significance ★ ⚠ same type
- ECD p.Arg188Leu Uncertain significance ★ ⚠ same type
- ECD p.Arg244Gln 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/sem1-p-glu61 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown