Is KMT2B p.Pro103Arg (c.308C>G) pathogenic?

KMT2B p.Pro103Arg (c.308C>G) is classified Benign in KMT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-31). AlphaMissense: likely benign (0.1119); Very rare (popmax 0.00155%, afr).

How common is KMT2B p.Pro103Arg (c.308C>G) in the general population?

KMT2B p.Pro103Arg (c.308C>G) is very rare (popmax 0.00155%, afr) (gnomAD).

What do computational predictors say about KMT2B p.Pro103Arg (c.308C>G)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

KMT2B p.Pro103Arg

c.308C>G · VCV4703015

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00155%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.219	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 -0.13	GERP -3.3, phastCons 0.21
Regional constraint	o/e 1.07	unconstrained · MANE · 4,448 bp · p 0.014 · regional, not allelic
Overall
CADD	10.77	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00155% African / African-American · 1/64,560 alleles

Overall 0.00016% 2/1,249,726 alleles · very rare exomes 1/1,098,174 · genomes 1/151,552 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00155%	64,560
European (non-Finnish)	0.000101%	989,962

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: KMT2B
Protein: p.Pro103Arg
Coding: c.308C>G
MANE Select: NM_014727
Type: single nucleotide variant
Location: chr19:35718326 (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.Pro103Ser Uncertain significance ★ ⚠ 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-pro103arg (accessed [today's date]).

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