SRRM2 p.Ser300=
c.900A>C · VCV4281013
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0083%, 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 |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.3 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 8.438 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0083%
European (non-Finnish) · 98/1,180,026 alleles
Filtering AF
0.00697%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00641%
Overall
0.00651%
105/1,613,968 alleles · very rare
exomes 102/1,461,854 · genomes 3/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0083% | 12,041 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| Admixed American | 0.00333% | 30,001 |
| South Asian | 0.0022% | 45,540 |
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
- SRRM2
- Protein
- p.Ser300=
- Coding
- c.900A>C
- MANE Select
- NM_016333
- Type
- single nucleotide variant
- Location
- chr16:2760367 (GRCh38)
- Gene constraint
- LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Residue 300
- the 'disordered' region; a UniProt-annotated variant site (in mrd72; likely pathogenic); a modified residue (phosphoserine)
Similar variants
- SRRM2 p.Arg1836Ter Pathogenic ★★ same type
- SRRM2 p.Arg1875Ter Pathogenic/Likely pathogenic ★★ same type
- SRRM2 p.Arg280Ter Pathogenic ★★ same type
- SRRM2 p.Arg628Ter Pathogenic ★★ same type
- SRRM2 p.Ala2245Val Uncertain significance ★★ same type
- SRRM2 p.Arg1213Gly Uncertain significance ★★ ⚠ same type
- SRRM2 p.Arg1723Lys Uncertain significance ★★ ⚠ same type
- SRRM2 p.Arg1971Gln 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/srrm2-p-ser300 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown