MMS19 p.Ala656=
c.1968C>T · rs145691255 · VCV720164
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0813%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.079 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.6 | GERP -4.3, phastCons 1 |
| Overall | ||
| CADD | 8.447 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0813%
European (non-Finnish) · 959/1,179,872 alleles
Filtering AF
0.077%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0752%
Overall
0.0636%
1,026/1,613,796 alleles · ultra-rare
exomes 958/1,461,682 · genomes 68/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0813% | 1,230 |
| Remaining individualsnot grpmax-eligible | 0.0512% | 1,952 |
| Admixed American | 0.03% | 3,333 |
| Finnishnot grpmax-eligible | 0.0109% | 9,144 |
| African / African-American | 0.0107% | 9,361 |
| 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
- MMS19
- Protein
- p.Ala656=
- Coding
- c.1968C>T
- MANE Select
- NM_022362
- dbSNP
- rs145691255
- Type
- single nucleotide variant
- Location
- chr10:97462627 (GRCh38)
- Gene constraint
- LOEUF 0.787 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.00
Similar variants
- MMS19 p.Gln409Pro Benign ★★ same type
- MMS19 p.Ala11Val Uncertain significance ★ ⚠ same type
- MMS19 p.Ala121Ser Uncertain significance ★ ⚠ same type
- MMS19 p.Ala2Val Uncertain significance ★ ⚠ same type
- MMS19 p.Ala324Val Uncertain significance ★ ⚠ same type
- MMS19 p.Ala383Val Uncertain significance ★ ⚠ same type
- MMS19 p.Ala3Val Uncertain significance ★ ⚠ same type
- MMS19 p.Ala4Thr 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/mms19-p-ala656 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown