Is KMT2D p.Pro2717Ser (c.8149C>T) pathogenic?

KMT2D p.Pro2717Ser (c.8149C>T) is classified Benign/Likely benign in KMT2D (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.069); Rare (popmax 0.508%, afr); Associated with Kabuki syndrome 1.

What condition is associated with KMT2D p.Pro2717Ser (c.8149C>T)?

KMT2D p.Pro2717Ser (c.8149C>T) is associated with Kabuki syndrome 1 (ClinVar).

How common is KMT2D p.Pro2717Ser (c.8149C>T) in the general population?

KMT2D p.Pro2717Ser (c.8149C>T) is rare (popmax 0.508%, afr) (gnomAD).

What do computational predictors say about KMT2D p.Pro2717Ser (c.8149C>T)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

KMT2D p.Pro2717Ser

c.8149C>T · rs201336660 · VCV716432

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.508%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Kabuki syndrome 1

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.154	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -3.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,746 bp · p 0.031 · regional, not allelic
Overall
CADD	17.05	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 0.508% African / African-American · 381/75,030 alleles

Filtering AF 0.466% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.449%

Overall 0.027% 436/1,612,222 alleles · rare exomes 213/1,459,870 · genomes 223/152,352 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.508%	197
Admixed American	0.0484%	2,065
Remaining individualsnot grpmax-eligible	0.0368%	2,714
Middle Eastern	0.0165%	6,056
European (non-Finnish)	0.00017%	589,640

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: KMT2D
Protein: p.Pro2717Ser
Coding: c.8149C>T
MANE Select: NM_003482
dbSNP: rs201336660
Type: single nucleotide variant
Location: chr12:49039515 (GRCh38)
Gene constraint: LOEUF 0.141 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 2717: a UniProt-annotated variant site (in kabuk1); the 'disordered' region

Full KMT2D gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Kabuki syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

KMT2D p.Pro2717= Likely benign ★ same residue
KMT2D c.10740+1G>A Pathogenic ★★ same condition
KMT2D c.14075+1G>A Pathogenic/Likely pathogenic ★★ same condition
KMT2D c.14251+1G>C Likely pathogenic ★★ same condition
KMT2D c.16338+1G>T Pathogenic/Likely pathogenic ★★ same condition
KMT2D c.16338+2T>C Pathogenic/Likely pathogenic ★★ same condition
KMT2D c.177-2A>G Pathogenic/Likely pathogenic ★★ same condition
KMT2D p.Arg1702Ter 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/kmt2d-p-pro2717ser (accessed [today's date]).

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