KMT2C p.Pro499=
c.1497A>G · rs573551117 · VCV2992838
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
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 -0.4 | GERP 0.77 |
| Overall | ||
| CADD | 11.02 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,876 alleles
Overall
0.000124%
2/1,611,776 alleles · very rare
exomes 1/1,459,438 · genomes 1/152,338 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,876 |
| European (non-Finnish) | 8.48e-05% | 1,178,800 |
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
- KMT2C
- Protein
- p.Pro499=
- Coding
- c.1497A>G
- MANE Select
- NM_170606
- dbSNP
- rs573551117
- Type
- single nucleotide variant
- Location
- chr7:152252063 (GRCh38)
- Gene constraint
- LOEUF 0.202 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Similar variants
- KMT2C c.1013-1G>A Pathogenic/Likely pathogenic ★★ same type
- KMT2C c.14344-1G>A Pathogenic/Likely pathogenic ★★ same type
- KMT2C p.Arg1481Ter Pathogenic/Likely pathogenic ★★ same type
- KMT2C p.Arg1906Ter Pathogenic ★★ same type
- KMT2C p.Arg2066Ter Pathogenic ★★ same type
- KMT2C p.Arg2609Ter Pathogenic/Likely pathogenic ★★ same type
- KMT2C p.Arg2610Ter Pathogenic/Likely pathogenic ★★ same type
- KMT2C p.Arg3079Ter Pathogenic ★★ 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/kmt2c-p-pro499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown