Is KMT2A p.Ser86Pro (c.256T>C) pathogenic?

KMT2A p.Ser86Pro (c.256T>C) is classified Uncertain significance in KMT2A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.1485); Very rare (popmax 0.00227%, eas); Associated with Inborn genetic diseases.

What condition is associated with KMT2A p.Ser86Pro (c.256T>C)?

KMT2A p.Ser86Pro (c.256T>C) is associated with Inborn genetic diseases (ClinVar).

How common is KMT2A p.Ser86Pro (c.256T>C) in the general population?

KMT2A p.Ser86Pro (c.256T>C) is very rare (popmax 0.00227%, eas) (gnomAD).

What do computational predictors say about KMT2A p.Ser86Pro (c.256T>C)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

KMT2A p.Ser86Pro

c.256T>C · rs1555138683 · VCV3115962

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00227%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.1	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 36 kb · p 1.2e-05 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00227% East Asian · 1/44,046 alleles

Overall 6.89e-05% 1/1,451,710 alleles · very rare

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.Ser86Pro
Coding: c.256T>C
MANE Select: NM_001197104
dbSNP: rs1555138683
Type: single nucleotide variant
Location: chr11:118436768 (GRCh38)
Gene constraint: LOEUF 0.065 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 86: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KMT2A p.Ser86Leu Uncertain significance ★ ⚠ same residue
KMT2A p.Ser86Thr Uncertain significance ★ ⚠ same residue
KMT2A p.Arg1101Ter Pathogenic/Likely pathogenic ★★ same condition
KMT2A p.Arg1151Ter Pathogenic ★★ same condition
KMT2A p.Arg1264Ter Pathogenic ★★ same condition
KMT2A p.Arg1502Ter Pathogenic ★★ same condition
KMT2A p.Arg1963Ter Pathogenic/Likely pathogenic ★★ same condition
KMT2A p.Arg1979Ter Pathogenic ★★ same condition

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-ser86pro (accessed [today's date]).

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