Is CD72 p.Gly236Arg (c.706G>C) pathogenic?

CD72 p.Gly236Arg (c.706G>C) is classified Uncertain significance in CD72 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-21). AlphaMissense: likely pathogenic (0.7005); Very rare (popmax 0.000339%, nfe).

How common is CD72 p.Gly236Arg (c.706G>C) in the general population?

CD72 p.Gly236Arg (c.706G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CD72 p.Gly236Arg (c.706G>C)?

AlphaMissense predicts likely pathogenic (score 0.7005) — an in-silico prediction, not a clinical call.

CD72 p.Gly236Arg

c.706G>C · VCV4223021

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7005 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7005	likely pathogenic · top 9% in CD72
REVEL	0.244	benign-leaning
SaProt	LLR -6.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.48, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 7,676 bp · p 0.39 · regional, not allelic
Overall
CADD	22.8	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 0.000339% European (non-Finnish) · 4/1,178,316 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,611,698 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: CD72
Protein: p.Gly236Arg
Coding: c.706G>C
MANE Select: NM_001782
Type: single nucleotide variant
Location: chr9:35612976 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.85
Residue 236: the c-type lectin domain; a disulfide bond

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-gly236arg (accessed [today's date]).

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