Is FOXK1 p.Pro23= (c.69A>C) pathogenic?

FOXK1 p.Pro23= (c.69A>C) is classified Likely benign in FOXK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-01). Rare (popmax 0.546%, amr).

How common is FOXK1 p.Pro23= (c.69A>C) in the general population?

FOXK1 p.Pro23= (c.69A>C) is rare (popmax 0.546%, amr) (gnomAD).

FOXK1 p.Pro23=

c.69A>C · VCV4083876

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.546%, amr)

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 -2.4	GERP -1.2
Overall
CADD	9.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.546% Admixed American · 86/15,742 alleles

Filtering AF 0.453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.419%

Overall 0.404% 3,967/982,650 alleles · rare exomes 3,452/837,468 · genomes 515/145,182 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.62%	62
Finnishnot grpmax-eligible	0.679%	147
Admixed Americangrpmax	0.546%	183
European (non-Finnish)	0.425%	235
Remaining individualsnot grpmax-eligible	0.394%	254
African / African-American	0.0586%	1,707
South Asian	0.0135%	7,389

Ashkenazi Jewish 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: FOXK1
Protein: p.Pro23=
Coding: c.69A>C
MANE Select: NM_001037165
Type: single nucleotide variant
Location: chr7:4682377 (GRCh38)
Gene constraint: LOEUF 0.664 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 58.39 · 1 PDB
Residue 23: the 'interaction with sin3a and sin3b' region

Full FOXK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

FOXK1 p.Ala724= Benign ★★ same type
FOXK1 p.Ala107Val Uncertain significance ★ ⚠ same type
FOXK1 p.Ala287Thr Uncertain significance ★ ⚠ same type
FOXK1 p.Ala287Val Uncertain significance ★ ⚠ same type
FOXK1 p.Ala321Thr Uncertain significance ★ ⚠ same type
FOXK1 p.Ala387Gly Uncertain significance ★ ⚠ same type
FOXK1 p.Ala42Thr Uncertain significance ★ ⚠ same type
FOXK1 p.Ala44Thr 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/foxk1-p-pro23 (accessed [today's date]).

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