Is CD79A p.Leu46Pro (c.137T>C) pathogenic?

CD79A p.Leu46Pro (c.137T>C) is classified Uncertain significance in CD79A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-09). AlphaMissense: likely benign (0.0875); Very rare (popmax 0.000513%, nfe); Associated with agammaglobulinemia 3, autosomal recessive.

What condition is associated with CD79A p.Leu46Pro (c.137T>C)?

CD79A p.Leu46Pro (c.137T>C) is associated with agammaglobulinemia 3, autosomal recessive (ClinVar).

How common is CD79A p.Leu46Pro (c.137T>C) in the general population?

CD79A p.Leu46Pro (c.137T>C) is very rare (popmax 0.000513%, nfe) (gnomAD).

What do computational predictors say about CD79A p.Leu46Pro (c.137T>C)?

AlphaMissense predicts likely benign (score 0.0875) — an in-silico prediction, not a clinical call.

CD79A p.Leu46Pro

c.137T>C · rs2074204859 · VCV1025028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0875 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000513%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 3, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0875	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -8.37	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 -0.28	GERP -2.2
Regional constraint	o/e 0.79	unconstrained · MANE · 3,672 bp · p 0.00029 · regional, not allelic
Overall
CADD	8.259	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 0.000513% European (non-Finnish) · 6/1,168,598 alleles

Filtering AF 0.000185% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000415% 6/1,444,808 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: CD79A
Protein: p.Leu46Pro
Coding: c.137T>C
MANE Select: NM_001783
dbSNP: rs2074204859
Type: single nucleotide variant
Location: chr19:41879047 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.56 · 6 PDB
Residue 46: 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.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
CD79A p.Gly179Arg Uncertain significance ★★ ⚠ same condition
CD79A p.Ile151Thr 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-leu46pro (accessed [today's date]).

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