ROM1 p.Arg193=
c.577C>A · rs754473229 · VCV1035964
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0061%, 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 |
|---|---|---|
| Pangolin | Δ0.23 | loss · gain 0.01 · not in the SpliceAI release · independent |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 0.46, phastCons 1 |
| Overall | ||
| CADD | 6.891 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0061%
European (non-Finnish) · 72/1,179,910 alleles
Filtering AF
0.00495%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00455%
Overall
0.00452%
73/1,613,880 alleles · very rare
exomes 73/1,461,670 · genomes 0/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0061% | 16,388 |
| Admixed American | 0.00167% | 60,012 |
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
- ROM1
- Protein
- p.Arg193=
- Coding
- c.577C>A
- MANE Select
- NM_000327
- dbSNP
- rs754473229
- Type
- single nucleotide variant
- Location
- chr11:62613858 (GRCh38)
- Gene constraint
- LOEUF 1.003 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.56 · 1 PDB
Similar variants
- ROM1 p.Arg193Gln Uncertain significance ★★ ⚠ same residue
- ROM1 p.Arg193Gly Uncertain significance ★★ ⚠ same residue
- ROM1 p.Arg193Trp Uncertain significance ★ ⚠ same residue
- ROM1 p.Ala132Val Uncertain significance ★★ ⚠ same type
- ROM1 p.Ala140Thr Uncertain significance ★★ ⚠ same type
- ROM1 p.Ala265Thr Uncertain significance ★★ ⚠ same type
- ROM1 p.Ala329Val Uncertain significance ★★ ⚠ same type
- ROM1 p.Ala54Thr 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/rom1-p-arg193 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown