Is KMT2B p.Ser320Phe (c.959C>T) pathogenic?

KMT2B p.Ser320Phe (c.959C>T) is classified Uncertain significance in KMT2B (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.174); Very rare (popmax 0.000509%, nfe); Associated with Inborn genetic diseases.

What condition is associated with KMT2B p.Ser320Phe (c.959C>T)?

KMT2B p.Ser320Phe (c.959C>T) is associated with Inborn genetic diseases (ClinVar).

How common is KMT2B p.Ser320Phe (c.959C>T) in the general population?

KMT2B p.Ser320Phe (c.959C>T) is very rare (popmax 0.000509%, nfe) (gnomAD).

What do computational predictors say about KMT2B p.Ser320Phe (c.959C>T)?

AlphaMissense predicts likely benign (score 0.174) — an in-silico prediction, not a clinical call.

KMT2B p.Ser320Phe

c.959C>T · VCV4044429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.174 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000509%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.174	likely benign
REVEL	0.343	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 4,448 bp · p 0.014 · regional, not allelic
Overall
CADD	23.5	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 0.000509% European (non-Finnish) · 6/1,179,676 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000372% 6/1,613,060 alleles · very rare exomes 5/1,460,922 · genomes 1/152,138 · 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: KMT2B
Protein: p.Ser320Phe
Coding: c.959C>T
MANE Select: NM_014727
Type: single nucleotide variant
Location: chr19:35720306 (GRCh38)
Gene constraint: LOEUF 0.127 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Residue 320: the 'disordered' region; a UniProt-annotated variant site (in dyt28)

Full KMT2B 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

KMT2B p.Ser320Thr Uncertain significance ★★ ⚠ same residue
KMT2B p.Ser320= Likely benign ★ same residue
KMT2B p.Gln1134Ter Pathogenic ★★ same condition
KMT2B p.Ala27Val Uncertain significance ★★ ⚠ same condition
KMT2B p.Ala40Thr Uncertain significance ★★ ⚠ same condition
KMT2B p.Ala66Val Uncertain significance ★★ same condition
KMT2B p.Ala752Glu Uncertain significance ★★ ⚠ same condition
KMT2B p.Arg1055Trp Uncertain significance ★★ 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/kmt2b-p-ser320phe (accessed [today's date]).

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