Is FOXE1 p.Lys95= (c.285A>G) pathogenic?

FOXE1 p.Lys95= (c.285A>G) is classified Benign/Likely benign in FOXE1 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2023-12-01). Rare (popmax 0.424%, nfe); Associated with Bamforth-Lazarus syndrome.

What condition is associated with FOXE1 p.Lys95= (c.285A>G)?

FOXE1 p.Lys95= (c.285A>G) is associated with Bamforth-Lazarus syndrome (ClinVar).

How common is FOXE1 p.Lys95= (c.285A>G) in the general population?

FOXE1 p.Lys95= (c.285A>G) is rare (popmax 0.424%, nfe) (gnomAD).

FOXE1 p.Lys95=

c.285A>G · rs139551528 · VCV435238

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.424%, nfe)

Conditions

Bamforth-Lazarus syndrome

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 -2.2	GERP -4.3
Overall
CADD	8.884	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.424% European (non-Finnish) · 4,998/1,179,660 alleles

Filtering AF 0.414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.41%

Overall 0.344% 5,554/1,612,922 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.424%	236
Ashkenazi Jewishnot grpmax-eligible	0.287%	348
Admixed American	0.268%	373
Remaining individualsnot grpmax-eligible	0.208%	481
Finnishnot grpmax-eligible	0.183%	547
Middle Eastern	0.149%	673
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.0614%	1,629
South Asian	0.00878%	11,384

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: FOXE1
Protein: p.Lys95=
Coding: c.285A>G
MANE Select: NM_004473
dbSNP: rs139551528
Type: single nucleotide variant
Location: chr9:97854199 (GRCh38)
Gene constraint: LOEUF 1.926 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.02
Residue 95: a DNA-binding region

Full FOXE1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Bamforth-Lazarus syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FOXE1 p.Lys95Gln Uncertain significance ★ ⚠ same residue
FOXE1 p.Ala118Val Uncertain significance ★★ ⚠ same condition
FOXE1 p.Leu129= Benign ★★ same condition
FOXE1 p.Ser275= Benign ★★ same condition
FOXE1 p.Ala168Thr Uncertain significance ★ ⚠ same condition
FOXE1 p.Ala178Val Uncertain significance ★ ⚠ same condition
FOXE1 p.Ala248Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
FOXE1 p.Glu85Ter 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/foxe1-p-lys95 (accessed [today's date]).

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