Is KMT2A p.Pro36= (c.108G>T) pathogenic?

KMT2A p.Pro36= (c.108G>T) is classified Likely benign in KMT2A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-22). Very rare (popmax 0.00128%, nfe).

How common is KMT2A p.Pro36= (c.108G>T) in the general population?

KMT2A p.Pro36= (c.108G>T) is very rare (popmax 0.00128%, nfe) (gnomAD).

KMT2A p.Pro36=

c.108G>T · VCV3615339

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00128%, 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 1.7	GERP -0.18, phastCons 1
Overall
CADD	12.23	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00128% European (non-Finnish) · 12/936,694 alleles

Filtering AF 0.000683% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00054%

Overall 0.00104% 12/1,157,540 alleles · very rare exomes 12/1,008,358 · genomes 0/149,182 · 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: KMT2A
Protein: p.Pro36=
Coding: c.108G>T
MANE Select: NM_001197104
Type: single nucleotide variant
Location: chr11:118436620 (GRCh38)
Gene constraint: LOEUF 0.065 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 36: the 'disordered' region

Full KMT2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KMT2A p.Pro36Gln Uncertain significance ★ same residue
KMT2A p.Pro36Leu Uncertain significance ★ ⚠ same residue
KMT2A c.10835+1G>A Likely pathogenic ★★ same type
KMT2A c.11071+1G>A Pathogenic ★★ same type
KMT2A c.4012+1G>C Pathogenic ★★ same type
KMT2A c.502+1G>A Pathogenic ★★ same type
KMT2A c.6079+2T>C Likely pathogenic ★★ same type
KMT2A p.Arg1064Ter 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/kmt2a-p-pro36 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown