Is CD79B p.Leu91Pro (c.272T>C) pathogenic?

CD79B p.Leu91Pro (c.272T>C) is classified Uncertain significance in CD79B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-07). AlphaMissense: likely benign (0.0743); Ultra-rare (popmax 0.0604%, sas); Associated with agammaglobulinemia 6, autosomal recessive.

What condition is associated with CD79B p.Leu91Pro (c.272T>C)?

CD79B p.Leu91Pro (c.272T>C) is associated with agammaglobulinemia 6, autosomal recessive (ClinVar).

How common is CD79B p.Leu91Pro (c.272T>C) in the general population?

CD79B p.Leu91Pro (c.272T>C) is ultra-rare (popmax 0.0604%, sas) (gnomAD).

What do computational predictors say about CD79B p.Leu91Pro (c.272T>C)?

AlphaMissense predicts likely benign (score 0.0743) — an in-silico prediction, not a clinical call.

CD79B p.Leu91Pro

c.272T>C · rs779639084 · VCV847658

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0743 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0604%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

agammaglobulinemia 6, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.0743	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.55	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 -5.3	GERP -4.2
Regional constraint	o/e 0.73	unconstrained · MANE · 3,032 bp · p 2.7e-06 · regional, not allelic
Overall
CADD	0.007	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 0.0604% South Asian · 55/91,094 alleles

Filtering AF 0.0476% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.043%

Overall 0.0057% 92/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0604%	1,656
Middle Eastern	0.0164%	6,084
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.0028%	35,758
African / African-American	0.00133%	74,914

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: CD79B
Protein: p.Leu91Pro
Coding: c.272T>C
MANE Select: NM_000626
dbSNP: rs779639084
Type: single nucleotide variant
Location: chr17:63930232 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 6 PDB
Residue 91: a disulfide bond; an α-helix; the ig-like v-type domain

Full CD79B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

agammaglobulinemia 6, autosomal recessive — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD79B p.Ala5Val Uncertain significance ★★ ⚠ same condition
CD79B p.Arg36Trp Uncertain significance ★★ ⚠ same condition
CD79B p.Gly216Arg Uncertain significance ★★ ⚠ same condition
CD79B p.Met96Val Uncertain significance ★★ ⚠ same condition
CD79B p.Thr212Met Uncertain significance ★★ ⚠ same condition
CD79B p.Val175Met Uncertain significance ★★ ⚠ same condition
CD79B c.118+12C>T Benign/Likely benign ★★ same condition
CD79B c.118+19C>T Likely benign ★★ 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/cd79b-p-leu91pro (accessed [today's date]).

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