Is KLF1 p.Pro85= (c.255G>A) pathogenic?

KLF1 p.Pro85= (c.255G>A) is classified Uncertain significance in KLF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00135%, afr); Associated with congenital dyserythropoietic anemia type 4.

What condition is associated with KLF1 p.Pro85= (c.255G>A)?

KLF1 p.Pro85= (c.255G>A) is associated with congenital dyserythropoietic anemia type 4 (ClinVar).

How common is KLF1 p.Pro85= (c.255G>A) in the general population?

KLF1 p.Pro85= (c.255G>A) is very rare (popmax 0.00135%, afr) (gnomAD).

How is Congenital dyserythropoietic anemia type IV inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

KLF1 p.Pro85=

c.255G>A · rs886054238 · VCV328324

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

congenital dyserythropoietic anemia type 4

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 -5.8	GERP -3
Overall
CADD	5.537	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00135% African / African-American · 1/74,260 alleles

Filtering AF 6.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000253% 4/1,583,678 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	74,260
European (non-Finnish)	0.000257%	388,567

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: KLF1
Protein: p.Pro85=
Coding: c.255G>A
MANE Select: NM_006563
dbSNP: rs886054238
Type: single nucleotide variant
Location: chr19:12885975 (GRCh38)
Gene constraint: LOEUF 1.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.11 · 3 PDB
Residue 85: a UniProt-annotated variant site (in cdan4b; likely pathogenic); the 'disordered' region

Full KLF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital dyserythropoietic anemia type 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital dyserythropoietic anemia type IV (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

KLF1 p.Pro85Gln Uncertain significance ★ ⚠ same residue
KLF1 p.Ala298Pro Pathogenic ★★ same condition
KLF1 c.*263C>T Uncertain significance ★★ same condition
KLF1 p.Arg137Cys Uncertain significance ★★ ⚠ same condition
KLF1 p.Arg360His Uncertain significance ★★ ⚠ same condition
KLF1 c.*277C>T Benign ★★ same condition
KLF1 c.*296G>A Benign ★★ same condition
KLF1 p.Leu96= Benign/Likely benign ★★ 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/klf1-p-pro85 (accessed [today's date]).

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