Is KLF11 p.Val75= (c.225C>T) pathogenic?

KLF11 p.Val75= (c.225C>T) is classified Benign/Likely benign in KLF11 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-23). Rare (popmax 0.553%, afr); Associated with maturity-onset diabetes of the young type 7.

What condition is associated with KLF11 p.Val75= (c.225C>T)?

KLF11 p.Val75= (c.225C>T) is associated with maturity-onset diabetes of the young type 7 (ClinVar).

How common is KLF11 p.Val75= (c.225C>T) in the general population?

KLF11 p.Val75= (c.225C>T) is rare (popmax 0.553%, afr) (gnomAD).

How is MODY inherited?

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

KLF11 p.Val75=

c.225C>T · rs144083374 · VCV1316948

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.553%, afr)

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 0.069	GERP -0.84, phastCons 0.43
Overall
CADD	7.399	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.553% African / African-American · 415/75,054 alleles

Filtering AF 0.509% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.492%

Overall 0.0299% 483/1,614,210 alleles · rare exomes 267/1,461,880 · genomes 216/152,330 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.553%	181
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0416%	2,404
Admixed American	0.0283%	3,530
South Asian	0.00439%	22,772
European (non-Finnish)	0.00153%	65,558

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.Val75=
Coding: c.225C>T
MANE Select: NM_003597
dbSNP: rs144083374
Type: single nucleotide variant
Location: chr2:10046332 (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-val75 (accessed [today's date]).

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