KMT2C p.Pro335=
c.1005T>A · rs141993954 · VCV1638599
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.549%, sas)
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 0.23 | GERP -0.2, phastCons 0.3 |
| Overall | ||
| CADD | 8.387 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.549%
South Asian · 435/79,248 alleles
Filtering AF
0.506%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.49%
Overall
0.241%
3,537/1,468,576 alleles · rare
exomes 3,412/1,323,470 · genomes 125/145,106 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.549% | 182 |
| Ashkenazi Jewishnot grpmax-eligible | 0.377% | 265 |
| Remaining individualsnot grpmax-eligible | 0.25% | 400 |
| European (non-Finnish) | 0.239% | 418 |
| Middle Eastern | 0.219% | 457 |
| Finnishnot grpmax-eligible | 0.196% | 510 |
| East Asian | 0.148% | 674 |
| Admixed American | 0.0913% | 1,095 |
| African / African-American | 0.0813% | 1,229 |
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.Pro335=
- Coding
- c.1005T>A
- MANE Select
- NM_170606
- dbSNP
- rs141993954
- Type
- single nucleotide variant
- Location
- chr7:152273712 (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-pro335 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown