DMAC2L p.Arg24Thr
c.71G>C · rs1355345120 · VCV3082999
Computational evidence
| Protein change | ||
| AlphaMissense | 0.794 | likely pathogenic |
|---|---|---|
| REVEL | 0.871 | moderately pathogenic-leaning |
| SaProt | — | not scored · why |
| ⇒ AlphaMissense and REVEL both call this damaging; SaProt makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 2.8, phastCons 1 |
| Regional constraint | o/e 0.97 | unconstrained · MANE · 4,232 bp · p 0.63 · regional, not allelic |
| Overall | ||
| CADD | 28.5 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R39T vs ClinVar R24T) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,600 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,251 |
Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- DMAC2L
- Protein
- p.Arg24Thr
- Coding
- c.71G>C
- MANE Select
- NM_001382507
- dbSNP
- rs1355345120
- Type
- single nucleotide variant
- Location
- chr14:50321558 (GRCh38)
- Gene constraint
- LOEUF 1.315 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.27
- Residue 24
- the 'n-terminal domain' region
Similar variants
- DMAC2L p.Arg24Ile Uncertain significance ★ ⚠ same residue
- L2HGDH p.Pro24Ser Conflicting classifications of pathogenicity ★ ⚠ same residue
- L2HGDH p.Met1Val Pathogenic ★★ same type
- L2HGDH c.140+3G>C Uncertain significance ★★ same type
- L2HGDH p.Ala26Val Uncertain significance ★★ ⚠ same type
- L2HGDH p.Ser41Asn Uncertain significance ★★ ⚠ same type
- L2HGDH p.Ala20= Likely benign ★★ same type
- L2HGDH p.Leu18Arg Benign/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/dmac2l-p-arg24thr (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown