Is KLF1 p.Ser102Pro (c.304T>C) pathogenic?

KLF1 p.Ser102Pro (c.304T>C) is classified Benign in KLF1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.1756); Common (popmax 66.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with congenital dyserythropoietic anemia type 4.

What condition is associated with KLF1 p.Ser102Pro (c.304T>C)?

KLF1 p.Ser102Pro (c.304T>C) is associated with congenital dyserythropoietic anemia type 4 (ClinVar).

How is Congenital dyserythropoietic anemia type IV inherited?

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

What do computational predictors say about KLF1 p.Ser102Pro (c.304T>C)?

AlphaMissense predicts likely benign (score 0.1756) — an in-silico prediction, not a clinical call.

KLF1 p.Ser102Pro

Q: How common is KLF1 p.Ser102Pro (c.304T>C) in the general population?

KLF1 p.Ser102Pro (c.304T>C) is common (popmax 66.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.304T>C · rs2072597 · VCV260001

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1756 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 66.7%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital dyserythropoietic anemia type 4

Computational evidence

Protein change
AlphaMissense	0.1756	likely benign
REVEL	0.008	strongly benign-leaning
SaProt	LLR -5.02	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3
Regional constraint	o/e 0.99	unconstrained · MANE · 2,252 bp · p 0.75 · regional, not allelic
Overall
CADD	0.124	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 66.7% East Asian · 27,403/41,102 alleles

Filtering AF 66% ClinGen BA1/BS1 input FAF95, joint · FAF99 65.7%

Overall 32.8% 508,679/1,553,064 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	66.7%	1
African / African-American	43.6%	2
South Asian	43.2%	2
Finnishnot grpmax-eligible	36.7%	3
Admixed American	36.6%	3
Remaining individualsnot grpmax-eligible	34%	3
European (non-Finnish)	29.9%	3
Middle Eastern	27.4%	4
Ashkenazi Jewishnot grpmax-eligible	25.4%	4
Amishnot grpmax-eligible	20.8%	5

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.Ser102Pro
Coding: c.304T>C
MANE Select: NM_006563
dbSNP: rs2072597
Type: single nucleotide variant
Location: chr19:12885926 (GRCh38)
Gene constraint: LOEUF 1.777 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 58.11 · 3 PDB
Residue 102: a UniProt-annotated variant site (in cdan4b; likely pathogenic); a UniProt-annotated variant site (in); 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.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
KLF1 p.Phe182Leu 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-ser102pro (accessed [today's date]).

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