MLH3 p.Ser883=
c.2649C>T · rs2139558741 · VCV1794278
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000424%, 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 -4.5 | GERP -3.3 |
| Overall | ||
| CADD | 0.273 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,180,030 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00031%
5/1,614,094 alleles · very rare
exomes 5/1,461,842 · genomes 0/152,252 · joint denominator
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
- MLH3
- Protein
- p.Ser883=
- Coding
- c.2649C>T
- MANE Select
- NM_001040108
- dbSNP
- rs2139558741
- Type
- single nucleotide variant
- Location
- chr14:75047007 (GRCh38)
- Gene constraint
- LOEUF 0.735 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 56.14
Similar variants
- MLH3 p.Ser883Pro Uncertain significance ★ ⚠ same residue
- MLH3 p.Gln1360Ter Pathogenic ★★ same type
- MLH3 p.Gln423Ter Pathogenic ★★ same type
- MLH3 p.Ser626Ter Pathogenic ★★ same type
- MLH3 p.Tyr441Ter Pathogenic ★★ same type
- MLH3 c.3280+4A>G Uncertain significance ★★ same type
- MLH3 c.3379+4A>G Uncertain significance ★★ same type
- MLH3 c.3643+2T>C 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/mlh3-p-ser883 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown