Is FOXN1 p.Ser3= (c.9G>A) pathogenic?

FOXN1 p.Ser3= (c.9G>A) is classified Benign/Likely benign in FOXN1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-28). Rare (popmax 0.895%, afr); Associated with T-cell immunodeficiency, congenital alopecia, and nail dystrophy.

What condition is associated with FOXN1 p.Ser3= (c.9G>A)?

FOXN1 p.Ser3= (c.9G>A) is associated with T-cell immunodeficiency, congenital alopecia, and nail dystrophy (ClinVar).

How common is FOXN1 p.Ser3= (c.9G>A) in the general population?

FOXN1 p.Ser3= (c.9G>A) is rare (popmax 0.895%, afr) (gnomAD).

FOXN1 p.Ser3=

Q: How is Severe combined immunodeficiency due to FOXN1 deficiency inherited?

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

c.9G>A · rs146390262 · VCV468555

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.895%, afr)

Conditions

T-cell immunodeficiency, congenital alopecia, and nail dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.7	GERP -2.9
Overall
CADD	12.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.895% African / African-American · 671/74,970 alleles

Filtering AF 0.839% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.817%

Overall 0.0484% 780/1,612,554 alleles · rare exomes 365/1,460,408 · genomes 415/152,146 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.895%	112
Admixed American	0.075%	1,333
Remaining individualsnot grpmax-eligible	0.0513%	1,951
Middle Eastern	0.0508%	1,970
South Asian	0.00879%	11,381
East Asian	0.00446%	22,424
European (non-Finnish)	0.00161%	62,099

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: FOXN1
Protein: p.Ser3=
Coding: c.9G>A
MANE Select: NM_001369369
dbSNP: rs146390262
Type: single nucleotide variant
Location: chr17:28523978 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.44 · 2 PDB
Residue 3: the 'disordered' region

Full FOXN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

T-cell immunodeficiency, congenital alopecia, and nail dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Severe combined immunodeficiency due to FOXN1 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

FOXN1 p.Ser3Leu Uncertain significance ★ ⚠ same residue
FOXN1 p.Ser3fs Pathogenic ★ same residue
FOXN1 p.Arg114Ter Pathogenic ★★★ same condition
FOXN1 p.Arg255Ter Pathogenic ★★★ same condition
FOXN1 p.Arg320Trp Pathogenic ★★★ same condition
FOXN1 p.Cys82Ter Pathogenic ★★★ same condition
FOXN1 p.Gln474Ter Pathogenic ★★★ same condition
FOXN1 p.His321Arg Likely pathogenic ★★★ 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/foxn1-p-ser3 (accessed [today's date]).

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