Is FOXN1 p.Ser49= (c.147G>C) pathogenic?

FOXN1 p.Ser49= (c.147G>C) is classified Likely benign in FOXN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). Absent from gnomAD v4.1; Associated with T-cell immunodeficiency, congenital alopecia, and nail dystrophy.

What condition is associated with FOXN1 p.Ser49= (c.147G>C)?

FOXN1 p.Ser49= (c.147G>C) is associated with T-cell immunodeficiency, congenital alopecia, and nail dystrophy (ClinVar).

How common is FOXN1 p.Ser49= (c.147G>C) in the general population?

FOXN1 p.Ser49= (c.147G>C) is absent from gnomAD v4.1 (gnomAD).

FOXN1 p.Ser49=

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.147G>C · rs148006498 · VCV745503

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -10	GERP -3.6
Overall
CADD	0.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FOXN1
Protein: p.Ser49=
Coding: c.147G>C
MANE Select: NM_001369369
dbSNP: rs148006498
Type: single nucleotide variant
Location: chr17:28524526 (GRCh38)
Gene constraint: LOEUF 0.442 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 54.44 · 2 PDB
Residue 49: 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.Ser49Leu Uncertain significance ★ ⚠ 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
FOXN1 p.Leu325Pro 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-ser49 (accessed [today's date]).

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