MRPS35 p.Val223=
c.669G>A · VCV3296123
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.22%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.02 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.4 | GERP 0.79, phastCons 1 |
| Overall | ||
| CADD | 6.696 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.22%
African / African-American · 165/74,970 alleles
Filtering AF
0.193%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.182%
Overall
0.012%
194/1,611,910 alleles · rare
exomes 90/1,459,604 · genomes 104/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.22% | 454 |
| Remaining individualsnot grpmax-eligible | 0.0224% | 4,459 |
| Admixed American | 0.0183% | 5,453 |
| European (non-Finnish) | 0.000339% | 294,574 |
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
- MRPS35
- Protein
- p.Val223=
- Coding
- c.669G>A
- MANE Select
- NM_021821
- Type
- single nucleotide variant
- Location
- chr12:27737575 (GRCh38)
- Structure
- AlphaFold pLDDT 77.94 · 86 PDB
Similar variants
- MRPS35 p.Gly43Arg Benign ★★ same type
- MRPS35 p.Leu319= Benign ★★ same type
- MRPS28 p.Arg141Gln Uncertain significance ★ ⚠ same type
- MRPS28 p.Arg141Trp Uncertain significance ★ ⚠ same type
- MRPS28 p.Arg143Gln Uncertain significance ★ ⚠ same type
- MRPS28 p.Asn166Ile Uncertain significance ★ ⚠ same type
- MRPS28 p.Asp130His Uncertain significance ★ ⚠ same type
- MRPS28 p.Cys5Tyr 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/mrps35-p-val223 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown