ROM1 p.Ser221Ter
c.662C>G · rs2134423357 · VCV1497005
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
nonsense (stop-gain)
predicted LoF
gnomAD v4.1
Absent
absent from gnomAD v4.1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function |
|---|---|---|
| NMD | predicted | premature termination codon in exon 2 of 3 |
| REVEL | 0.489 | indeterminate |
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 4 | GERP 1.5, phastCons 0.98 |
| Overall | ||
| CADD | 39.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ROM1
- Protein
- p.Ser221Ter
- Coding
- c.662C>G
- MANE Select
- NM_000327
- dbSNP
- rs2134423357
- Type
- single nucleotide variant
- Location
- chr11:62614329 (GRCh38)
- Gene constraint
- LOEUF 1.003 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 86.56 · 1 PDB
Similar variants
- 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
- ROM1 p.Ala69Gly Uncertain significance ★★ ⚠ same type
- ROM1 p.Ala71Thr Uncertain significance ★★ ⚠ same type
- ROM1 p.Ala71Val 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-ser221ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown