ROS1 p.Ala1908=
c.5724C>T · VCV3770453
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 11%, amr) — too common for a highly-penetrant pathogenic allele
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 -1.6 | GERP -2.5 |
| Overall | ||
| CADD | 2.012 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
11%
Admixed American · 6,613/59,874 alleles
Filtering AF
10.8%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 10.7%
Overall
0.7%
11,294/1,613,684 alleles · common
exomes 9,541/1,461,510 · genomes 1,753/152,174 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 11% | 9 |
| East Asian | 7.11% | 14 |
| Ashkenazi Jewishnot grpmax-eligible | 1.55% | 64 |
| Remaining individualsnot grpmax-eligible | 0.854% | 117 |
| African / African-American | 0.228% | 439 |
| South Asian | 0.116% | 859 |
| Middle Eastern | 0.0495% | 2,020 |
| European (non-Finnish) | 0.018% | 5,565 |
| Finnishnot grpmax-eligible | 0.00781% | 12,802 |
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
- ROS1
- Protein
- p.Ala1908=
- Coding
- c.5724C>T
- MANE Select
- NM_001378902
- Type
- single nucleotide variant
- Location
- chr6:117321294 (GRCh38)
- Gene constraint
- LOEUF 0.993 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.86 · 5 PDB
Similar variants
- ROS1 p.Ala1908Thr Uncertain significance ★ ⚠ same residue
- ROS1 c.4126+3A>G Likely benign ★★ same type
- ROS1 p.Arg1500Gly Benign ★★ same type
- ROS1 p.Asp1770His Benign ★★ same type
- ROS1 p.Glu1896Lys Benign ★★ same type
- ROS1 p.Gly1022Asp Likely benign ★★ ⚠ same type
- ROS1 p.Leu1331= Benign/Likely benign ★★ same type
- ROS1 p.Leu755Ile Likely benign ★★ 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/ros1-p-ala1908 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown