Is CD79B p.Val175Met (c.523G>A) pathogenic?

CD79B p.Val175Met (c.523G>A) is classified Uncertain significance in CD79B (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-02-28). AlphaMissense: ambiguous (0.4484); Very rare (popmax 0.00223%, eas); Associated with CD79B-related disorder.

What condition is associated with CD79B p.Val175Met (c.523G>A)?

CD79B p.Val175Met (c.523G>A) is associated with CD79B-related disorder, agammaglobulinemia 6, autosomal recessive (ClinVar).

How common is CD79B p.Val175Met (c.523G>A) in the general population?

CD79B p.Val175Met (c.523G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD79B p.Val175Met (c.523G>A)?

AlphaMissense predicts ambiguous (score 0.4484) — an in-silico prediction, not a clinical call.

CD79B p.Val175Met

c.523G>A · rs148032848 · VCV2168046

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4484 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

CD79B-related disorder

Computational evidence

Protein change
AlphaMissense	0.4484	ambiguous
REVEL	0.556	indeterminate
SaProt	LLR -8.30	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 3,032 bp · p 2.7e-06 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,886 alleles

Filtering AF 0.000183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00012%

Overall 0.000558% 9/1,611,650 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,886
Admixed American	0.00167%	59,984
Remaining individualsnot grpmax-eligible	0.0016%	62,452
European (non-Finnish)	0.000509%	196,539

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.Val175Met
Coding: c.523G>A
MANE Select: NM_000626
dbSNP: rs148032848
Type: single nucleotide variant
Location: chr17:63929796 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.02 · 6 PDB
Residue 175: an α-helix

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

Disease context

CD79B-related disorder

Also linked: agammaglobulinemia 6, autosomal recessive

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.Leu91Pro Uncertain significance ★★ ⚠ same condition
CD79B p.Met96Val Uncertain significance ★★ ⚠ same condition
CD79B p.Thr212Met 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-val175met (accessed [today's date]).

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