Is CD79A p.Ile218Lys (c.653T>A) pathogenic?

CD79A p.Ile218Lys (c.653T>A) is classified Uncertain significance in CD79A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-12-11). AlphaMissense: likely pathogenic (0.6411); Very rare (popmax 0.00907%, eas); Associated with agammaglobulinemia 3, autosomal recessive.

What condition is associated with CD79A p.Ile218Lys (c.653T>A)?

CD79A p.Ile218Lys (c.653T>A) is associated with agammaglobulinemia 3, autosomal recessive (ClinVar).

How common is CD79A p.Ile218Lys (c.653T>A) in the general population?

CD79A p.Ile218Lys (c.653T>A) is very rare (popmax 0.00907%, eas) (gnomAD).

What do computational predictors say about CD79A p.Ile218Lys (c.653T>A)?

AlphaMissense predicts likely pathogenic (score 0.6411) — an in-silico prediction, not a clinical call.

CD79A p.Ile218Lys

c.653T>A · rs781969358 · VCV1054078

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6411 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00907%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

agammaglobulinemia 3, autosomal recessive

Computational evidence

Protein change
AlphaMissense	0.6411	likely pathogenic
REVEL	0.384	indeterminate
SaProt	LLR -4.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 3,672 bp · p 0.00029 · regional, not allelic
Overall
CADD	21.4	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 0.00907% East Asian · 4/44,082 alleles

Filtering AF 0.00302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00182%

Overall 0.000348% 5/1,435,614 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00907%	11,020
Remaining individualsnot grpmax-eligible	0.00162%	61,608

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.Ile218Lys
Coding: c.653T>A
MANE Select: NM_001783
dbSNP: rs781969358
Type: single nucleotide variant
Location: chr19:41880952 (GRCh38)
Gene constraint: LOEUF 0.991 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.56 · 6 PDB

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-ile218lys (accessed [today's date]).

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