Is FOXE1 p.Ser275= (c.825C>T) pathogenic?

FOXE1 p.Ser275= (c.825C>T) is classified Benign in FOXE1 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-05-08). Common (popmax 87.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Bamforth-Lazarus syndrome.

What condition is associated with FOXE1 p.Ser275= (c.825C>T)?

FOXE1 p.Ser275= (c.825C>T) is associated with Bamforth-Lazarus syndrome (ClinVar).

FOXE1 p.Ser275=

Q: How common is FOXE1 p.Ser275= (c.825C>T) in the general population?

FOXE1 p.Ser275= (c.825C>T) is common (popmax 87.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.825C>T · rs3021526 · VCV95098

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 87.9%, eas) — too common for a highly-penetrant pathogenic allele

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 -4.6	GERP -3.5
Overall
CADD	1.356	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 87.9% East Asian · 32,907/37,446 alleles

Filtering AF 87.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 86.8%

Overall 62.1% 903,873/1,456,554 alleles · common exomes 807,716/1,304,692 · genomes 96,157/151,862 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	87.9%	1
Admixed American	66.8%	1
African / African-American	66.4%	2
Finnishnot grpmax-eligible	63.9%	2
South Asian	62.2%	2
Remaining individualsnot grpmax-eligible	61.9%	2
European (non-Finnish)	61%	2
Middle Eastern	53.9%	2
Ashkenazi Jewishnot grpmax-eligible	48.7%	2
Amishnot grpmax-eligible	40.4%	2

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.Ser275=
Coding: c.825C>T
MANE Select: NM_004473
dbSNP: rs3021526
Type: single nucleotide variant
Location: chr9:97854739 (GRCh38)
Gene constraint: LOEUF 1.926 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 62.02

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.Ala118Val Uncertain significance ★★ ⚠ same condition
FOXE1 p.Leu129= Benign ★★ same condition
FOXE1 p.Lys95= Benign/Likely 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
FOXE1 p.Lys95Gln 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-ser275 (accessed [today's date]).

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