Is CD72 p.Lys146Arg (c.437A>G) pathogenic?

CD72 p.Lys146Arg (c.437A>G) is classified Uncertain significance in CD72 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-11). AlphaMissense: likely benign (0.0905); Ultra-rare (popmax 0.0468%, eas).

How common is CD72 p.Lys146Arg (c.437A>G) in the general population?

CD72 p.Lys146Arg (c.437A>G) is ultra-rare (popmax 0.0468%, eas) (gnomAD).

What do computational predictors say about CD72 p.Lys146Arg (c.437A>G)?

AlphaMissense predicts likely benign (score 0.0905) — an in-silico prediction, not a clinical call.

CD72 p.Lys146Arg

c.437A>G · rs769918063 · VCV2513628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0468%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0905	likely benign
REVEL	0.022	moderately benign-leaning
SaProt	LLR -6.97	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 -1.8	GERP -3.4
Regional constraint	o/e 0.96	unconstrained · MANE · 7,676 bp · p 0.39 · regional, not allelic
Overall
CADD	2.54	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 0.0468% East Asian · 21/44,888 alleles

Filtering AF 0.0313% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0263%

Overall 0.00144% 21/1,461,826 alleles · ultra-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: CD72
Protein: p.Lys146Arg
Coding: c.437A>G
MANE Select: NM_001782
dbSNP: rs769918063
Type: single nucleotide variant
Location: chr9:35616194 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.85

Full CD72 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD72 p.Ala180Glu Uncertain significance ★ ⚠ same type
CD72 p.Ala269Val Uncertain significance ★ ⚠ same type
CD72 p.Ala2Gly Uncertain significance ★ ⚠ same type
CD72 p.Ala4Thr Uncertain significance ★ ⚠ same type
CD72 p.Ala81Val Uncertain significance ★ ⚠ same type
CD72 p.Arg144Cys Uncertain significance ★ ⚠ same type
CD72 p.Arg161Lys Uncertain significance ★ ⚠ same type
CD72 p.Arg84Leu Uncertain significance ★ ⚠ same type

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/cd72-p-lys146arg (accessed [today's date]).

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