Is KLF11 p.Pro71Ser (c.211C>T) pathogenic?

KLF11 p.Pro71Ser (c.211C>T) is classified Uncertain significance in KLF11 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). AlphaMissense: likely pathogenic (0.6975); Very rare (popmax 0.000424%, nfe).

How common is KLF11 p.Pro71Ser (c.211C>T) in the general population?

KLF11 p.Pro71Ser (c.211C>T) is very rare (popmax 0.000424%, nfe) (gnomAD).

What do computational predictors say about KLF11 p.Pro71Ser (c.211C>T)?

AlphaMissense predicts likely pathogenic (score 0.6975) — an in-silico prediction, not a clinical call.

KLF11 p.Pro71Ser

c.211C>T · VCV4093311

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6975 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6975	likely pathogenic
REVEL	0.425	indeterminate
SaProt	LLR -6.23	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 8,787 bp · p 1.3e-05 · regional, not allelic
Overall
CADD	24.3	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 0.000424% European (non-Finnish) · 5/1,180,028 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,174 alleles · very rare exomes 5/1,461,876 · genomes 0/152,298 · 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.Pro71Ser
Coding: c.211C>T
MANE Select: NM_003597
Type: single nucleotide variant
Location: chr2:10046318 (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

Similar variants

KLF11 p.Pro71Ala Uncertain significance ★ same residue
KLF11 p.Pro71= Likely benign ★ same residue
KLF11 c.-104C>T Uncertain significance ★★ same type
KLF11 p.Ala146Val Uncertain significance ★★ ⚠ same type
KLF11 p.Ala321Pro Uncertain significance ★★ ⚠ same type
KLF11 p.Ala89Val Uncertain significance ★★ ⚠ same type
KLF11 p.Arg120Gly Uncertain significance ★★ ⚠ same type
KLF11 p.Arg390Gln Uncertain significance ★★ same type

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-pro71ser (accessed [today's date]).

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