SRP54 p.Phe396=
c.1188T>C · VCV4776582
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 0.61 | GERP -0.12, phastCons 1 |
| Overall | ||
| CADD | 9.22 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,026 alleles
Overall
0.000124%
2/1,613,882 alleles · very rare
exomes 2/1,461,588 · genomes 0/152,294 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,026 |
| European (non-Finnish) | 8.48e-05% | 1,179,924 |
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
- SRP54
- Protein
- p.Phe396=
- Coding
- c.1188T>C
- MANE Select
- NM_003136
- Type
- single nucleotide variant
- Location
- chr14:35022941 (GRCh38)
- Gene constraint
- LOEUF 0.304 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 79.68 · 9 PDB
- Residue 396
- the 'm-domain' region; an α-helix
Similar variants
- SRP54 p.Gly113Arg Likely pathogenic ★★ same type
- SRP54 p.Gly226Glu Pathogenic/Likely pathogenic ★★ same type
- SRP54 c.1423+4A>G Uncertain significance ★★ same type
- SRP54 c.1424-5T>G Uncertain significance ★★ same type
- SRP54 c.78+3A>G Uncertain significance ★★ same type
- SRP54 p.Arg15Cys Uncertain significance ★★ ⚠ same type
- SRP54 p.Gln404Glu Uncertain significance ★★ ⚠ same type
- SRP54 p.Ile246Val 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/srp54-p-phe396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown