Is CIITA p.Pro211fs (c.632del) pathogenic?

CIITA p.Pro211fs (c.632del) is classified Pathogenic/Likely pathogenic in CIITA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-04-22). Very rare (popmax 0.000339%, nfe); Associated with MHC class II deficiency 1.

What condition is associated with CIITA p.Pro211fs (c.632del)?

CIITA p.Pro211fs (c.632del) is associated with MHC class II deficiency 1, rheumatoid arthritis, MHC class II deficiency (ClinVar).

How common is CIITA p.Pro211fs (c.632del) in the general population?

CIITA p.Pro211fs (c.632del) is very rare (popmax 0.000339%, nfe) (gnomAD).

CIITA p.Pro211fs

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.632del · rs2144580551 · VCV1076559

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Conditions

MHC class II deficiency 1

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 8 of 20
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.9	GERP -4.5

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,050 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000274% 4/1,461,890 alleles · very rare

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: CIITA
Protein: p.Pro211fs
Coding: c.632del
MANE Select: NM_000246
dbSNP: rs2144580551
Type: Deletion
Location: chr16:10902660 (GRCh38)
Gene constraint: LOEUF 0.729 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.10

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

Disease context

MHC class II deficiency 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rheumatoid arthritis MHC class II deficiency

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CIITA p.Pro211Ser Uncertain significance ★★ ⚠ same residue
CIITA p.Pro211His Uncertain significance ★ ⚠ same residue
CIITA p.Pro211= Likely benign ★ 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 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-pro211fs (accessed [today's date]).

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