Is KLF11 p.Phe6= (c.18C>T) pathogenic?

KLF11 p.Phe6= (c.18C>T) is classified Uncertain significance in KLF11 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Very rare (popmax 0.000856%, nfe); Associated with maturity-onset diabetes of the young type 7.

What condition is associated with KLF11 p.Phe6= (c.18C>T)?

KLF11 p.Phe6= (c.18C>T) is associated with maturity-onset diabetes of the young type 7 (ClinVar).

How common is KLF11 p.Phe6= (c.18C>T) in the general population?

KLF11 p.Phe6= (c.18C>T) is very rare (popmax 0.000856%, nfe) (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

KLF11 p.Phe6=

c.18C>T · rs886054722 · VCV330621

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000856%, nfe)

Conditions

maturity-onset diabetes of the young type 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.2	GERP -1.7
Overall
CADD	5.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000856% European (non-Finnish) · 9/1,051,554 alleles

Filtering AF 0.000403% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000292%

Overall 0.000652% 9/1,379,590 alleles · very rare exomes 8/1,230,392 · genomes 1/149,198 · 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: KLF11
Protein: p.Phe6=
Coding: c.18C>T
MANE Select: NM_003597
dbSNP: rs886054722
Type: single nucleotide variant
Location: chr2:10043734 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.73

Full KLF11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

maturity-onset diabetes of the young type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

KLF11 c.-104C>T Uncertain significance ★★ same condition
KLF11 p.Ala146Val Uncertain significance ★★ ⚠ same condition
KLF11 p.Ala321Pro Uncertain significance ★★ ⚠ same condition
KLF11 p.Ala89Val Uncertain significance ★★ ⚠ same condition
KLF11 p.Arg120Gly Uncertain significance ★★ ⚠ same condition
KLF11 p.Arg390Gln Uncertain significance ★★ same condition
KLF11 p.Gln215Lys Uncertain significance ★★ ⚠ same condition
KLF11 p.Gly331Val 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/klf11-p-phe6 (accessed [today's date]).

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