Is CIITA p.Pro356= (c.1068G>A) pathogenic?

CIITA p.Pro356= (c.1068G>A) is classified Conflicting classifications of pathogenicity in CIITA (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). Rare (popmax 0.51%, mid); Associated with MHC class II deficiency.

What condition is associated with CIITA p.Pro356= (c.1068G>A)?

CIITA p.Pro356= (c.1068G>A) is associated with MHC class II deficiency (ClinVar).

How common is CIITA p.Pro356= (c.1068G>A) in the general population?

CIITA p.Pro356= (c.1068G>A) is rare (popmax 0.51%, mid) (gnomAD).

CIITA p.Pro356=

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.1068G>A · rs140486686 · VCV528793

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.51%, mid)

Conditions

MHC class II deficiency

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 -7.4	GERP -4.3
Overall
CADD	0.506	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.51% Middle Eastern · 27/5,294 alleles

Filtering AF 0.36% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.31%

Overall 0.0997% 1,609/1,613,160 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.51%	196
Remaining individualsnot grpmax-eligible	0.122%	821
Admixed American	0.115%	870
European (non-Finnish)	0.113%	883
South Asian	0.0538%	1,858
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
African / African-American	0.0373%	2,679
Finnishnot grpmax-eligible	0.0156%	6,395

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.Pro356=
Coding: c.1068G>A
MANE Select: NM_000246
dbSNP: rs140486686
Type: single nucleotide variant
Location: chr16:10906560 (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 — 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.Pro356Leu Uncertain significance ★★ ⚠ same residue
CIITA p.Pro356Arg Uncertain significance ★ ⚠ same residue
CIITA c.199+1G>A Likely pathogenic ★★ same condition
CIITA c.2888+1G>A Pathogenic/Likely pathogenic ★★ same condition
CIITA c.2889-1G>T Pathogenic/Likely pathogenic ★★ same condition
CIITA c.436+1G>A Likely pathogenic ★★ same condition
CIITA c.628+1G>A Likely pathogenic ★★ same condition
CIITA p.Arg308Ter Pathogenic/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-pro356 (accessed [today's date]).

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