Is KMT2B p.Pro103Ser (c.307C>T) pathogenic?

KMT2B p.Pro103Ser (c.307C>T) is classified Uncertain significance in KMT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-23). AlphaMissense: likely benign (0.0865); No allele count reported in gnomAD v4.1 (AN 1,250,028).

How common is KMT2B p.Pro103Ser (c.307C>T) in the general population?

KMT2B p.Pro103Ser (c.307C>T) is no allele count reported in gnomAD v4.1 (AN 1,250,028) (gnomAD).

What do computational predictors say about KMT2B p.Pro103Ser (c.307C>T)?

AlphaMissense predicts likely benign (score 0.0865) — an in-silico prediction, not a clinical call.

KMT2B p.Pro103Ser

c.307C>T · VCV3612636

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0865 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,250,028)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0865	likely benign
REVEL	0.207	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -0.56, phastCons 0.63
Regional constraint	o/e 1.07	unconstrained · MANE · 4,448 bp · p 0.014 · regional, not allelic
Overall
CADD	14.05	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,250,028). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: KMT2B
Protein: p.Pro103Ser
Coding: c.307C>T
MANE Select: NM_014727
Type: single nucleotide variant
Location: chr19:35718325 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 103: the 'disordered' region

Full KMT2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KMT2B p.Pro103Arg Benign ★ same residue
KMT2B p.Ala1616Val Likely pathogenic ★★ same type
KMT2B p.Ala2641Thr Likely pathogenic ★★ same type
KMT2B p.Arg142Ter Pathogenic ★★ same type
KMT2B p.Arg1597Trp Pathogenic/Likely pathogenic ★★ same type
KMT2B p.Arg1705Ter Pathogenic ★★ same type
KMT2B p.Arg2565Gly Likely pathogenic ★★ same type
KMT2B p.Arg2610Cys Likely 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/kmt2b-p-pro103ser (accessed [today's date]).

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