Is CIITA p.Pro211Ser (c.631C>T) pathogenic?

CIITA p.Pro211Ser (c.631C>T) is classified Uncertain significance in CIITA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-10). AlphaMissense: likely benign (0.0793); Very rare (popmax 0.00833%, amr); Associated with MHC class II deficiency.

What condition is associated with CIITA p.Pro211Ser (c.631C>T)?

CIITA p.Pro211Ser (c.631C>T) is associated with MHC class II deficiency, rheumatoid arthritis (ClinVar).

How common is CIITA p.Pro211Ser (c.631C>T) in the general population?

CIITA p.Pro211Ser (c.631C>T) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about CIITA p.Pro211Ser (c.631C>T)?

AlphaMissense predicts likely benign (score 0.0793) — an in-silico prediction, not a clinical call.

CIITA p.Pro211Ser

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.631C>T · rs201764329 · VCV1410833

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0793 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

MHC class II deficiency

Computational evidence

Protein change
AlphaMissense	0.0793	likely benign
REVEL	0.071	moderately benign-leaning
SaProt	LLR -6.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.88	GERP -4.5
Regional constraint	o/e 1.10	unconstrained · MANE · 46 kb · p 6.2e-05 · regional, not allelic
Overall
CADD	2.444	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,028 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00279%

Overall 0.00353% 57/1,614,240 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,006
Remaining individualsnot grpmax-eligible	0.0064%	15,628
European (non-Finnish)	0.00407%	24,584

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.Pro211Ser
Coding: c.631C>T
MANE Select: NM_000246
dbSNP: rs201764329
Type: single nucleotide variant
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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: rheumatoid arthritis

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

CIITA p.Pro211His Uncertain significance ★ ⚠ same residue
CIITA p.Pro211= Likely benign ★ same residue
CIITA p.Pro211fs Pathogenic/Likely pathogenic ★★ 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

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-pro211ser (accessed [today's date]).

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