Is KLF11 p.Pro117= (c.351A>G) pathogenic?

KLF11 p.Pro117= (c.351A>G) is classified Conflicting classifications of pathogenicity in KLF11 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-01). Very rare (popmax 0.000593%, nfe); Associated with maturity-onset diabetes of the young type 7.

What condition is associated with KLF11 p.Pro117= (c.351A>G)?

KLF11 p.Pro117= (c.351A>G) is associated with maturity-onset diabetes of the young type 7 (ClinVar).

How common is KLF11 p.Pro117= (c.351A>G) in the general population?

KLF11 p.Pro117= (c.351A>G) is very rare (popmax 0.000593%, nfe) (gnomAD).

How is MODY inherited?

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

KLF11 p.Pro117=

c.351A>G · rs781433096 · VCV894353

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000593%, 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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.3	GERP -3.2
Overall
CADD	0.227	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000593% European (non-Finnish) · 7/1,180,010 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,268 alleles · very rare exomes 8/1,461,130 · genomes 0/152,138 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,500
European (non-Finnish)grpmax	0.000593%	168,573

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro117=
Coding: c.351A>G
MANE Select: NM_003597
dbSNP: rs781433096
Type: single nucleotide variant
Location: chr2:10047688 (GRCh38)
Gene constraint: LOEUF 1.07 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 49.73
Residue 117: the 'disordered' region

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 p.Pro117Leu Uncertain significance ★ ⚠ same residue
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

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-pro117 (accessed [today's date]).

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