Is CD79A p.Thr75Met (c.224C>T) pathogenic?

CD79A p.Thr75Met (c.224C>T) is classified Uncertain significance in CD79A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-06). AlphaMissense: likely benign (0.3205); Ultra-rare (popmax 0.0944%, sas); Associated with agammaglobulinemia 3, autosomal recessive.

What condition is associated with CD79A p.Thr75Met (c.224C>T)?

CD79A p.Thr75Met (c.224C>T) is associated with agammaglobulinemia 3, autosomal recessive (ClinVar).

How common is CD79A p.Thr75Met (c.224C>T) in the general population?

CD79A p.Thr75Met (c.224C>T) is ultra-rare (popmax 0.0944%, sas) (gnomAD).

What do computational predictors say about CD79A p.Thr75Met (c.224C>T)?

AlphaMissense predicts likely benign (score 0.3205) — an in-silico prediction, not a clinical call.

CD79A p.Thr75Met

c.224C>T · rs199967393 · VCV835007

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3205 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0944%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 3, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.3205	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -8.63	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 0.7	GERP 0.7
Regional constraint	o/e 0.79	unconstrained · MANE · 3,672 bp · p 0.00029 · regional, not allelic
Overall
CADD	18.9	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 0.0944% South Asian · 86/91,088 alleles

Filtering AF 0.0782% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0723%

Overall 0.0218% 352/1,614,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0944%	1,059
Middle Eastern	0.033%	3,031
Admixed American	0.0316%	3,160
European (non-Finnish)	0.0199%	5,021
Remaining individualsnot grpmax-eligible	0.0096%	10,418
African / African-American	0.00533%	18,761

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: CD79A
Protein: p.Thr75Met
Coding: c.224C>T
MANE Select: NM_001783
dbSNP: rs199967393
Type: single nucleotide variant
Location: chr19:41879134 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.56 · 6 PDB
Residue 75: a disulfide bond; the ig-like c2-type domain

Full CD79A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

agammaglobulinemia 3, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD79A p.Thr75Lys Uncertain significance ★ ⚠ same residue
CD79A p.Thr75= Likely benign ★ same residue
CD79A p.Arg124Cys Uncertain significance ★★ ⚠ same condition
CD79A p.Arg124His Uncertain significance ★★ ⚠ same condition
CD79A p.Arg168Gln Uncertain significance ★★ ⚠ same condition
CD79A p.Arg204Gln Uncertain significance ★★ ⚠ same condition
CD79A p.Asn60Ser Uncertain significance ★★ ⚠ same condition
CD79A p.Asn63Ser Uncertain significance ★★ ⚠ 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/cd79a-p-thr75met (accessed [today's date]).

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