Is CIITA p.Phe501fs (c.1502_1511del) pathogenic?

CIITA p.Phe501fs (c.15021511del) is classified Pathogenic in CIITA (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-14). Absent from gnomAD; Associated with MHC class II deficiency.

What condition is associated with CIITA p.Phe501fs (c.1502_1511del)?

CIITA p.Phe501fs (c.1502_1511del) is associated with MHC class II deficiency (ClinVar).

How common is CIITA p.Phe501fs (c.1502_1511del) in the general population?

CIITA p.Phe501fs (c.1502_1511del) is absent from gnomAD (gnomAD).

CIITA p.Phe501fs

Q: How is Immunodeficiency by defective expression of MHC class II inherited?

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

c.1502_1511del · rs2144710452 · VCV1459331

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

MHC class II deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.2	GERP 1.2, phastCons 0.93

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CIITA
Protein: p.Phe501fs
Coding: c.1502_1511del
MANE Select: NM_000246
dbSNP: rs2144710452
Type: Deletion
Location: chr16:10906991 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.10
Residue 501: the nacht domain

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

Disease context

MHC class II deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency by defective expression of MHC class II (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CIITA p.Phe501= Likely benign ★★ same residue
CIITA p.Phe501Leu Uncertain significance ⚠ same residue
CIITA p.Ala656fs Pathogenic/Likely pathogenic ★★ same condition
CIITA p.Gln507fs Pathogenic/Likely pathogenic ★★ same condition
CIITA p.Gln764fs Pathogenic/Likely pathogenic ★★ same condition
CIITA p.Pro211fs Pathogenic/Likely pathogenic ★★ same condition
CIITA c.3150-19del Likely benign ★★ same condition
CIITA c.3147_3149+2del 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/ciita-p-phe501fs (accessed [today's date]).

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