Is CD72 p.Leu337Val (c.1009C>G) pathogenic?

CD72 p.Leu337Val (c.1009C>G) is classified Uncertain significance in CD72 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-10). AlphaMissense: likely benign (0.0796); Ultra-rare (popmax 0.0351%, sas).

How common is CD72 p.Leu337Val (c.1009C>G) in the general population?

CD72 p.Leu337Val (c.1009C>G) is ultra-rare (popmax 0.0351%, sas) (gnomAD).

What do computational predictors say about CD72 p.Leu337Val (c.1009C>G)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

CD72 p.Leu337Val

c.1009C>G · rs775851464 · VCV2595804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0351%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.057	moderately benign-leaning
SaProt	LLR -7.08	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 -20	GERP -3.9
Regional constraint	o/e 0.96	unconstrained · MANE · 7,676 bp · p 0.39 · regional, not allelic
Overall
CADD	0.001	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 0.0351% South Asian · 32/91,062 alleles

Filtering AF 0.0256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0222%

Overall 0.00242% 39/1,612,606 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0351%	2,846
Remaining individualsnot grpmax-eligible	0.0032%	31,209
European (non-Finnish)	0.000424%	235,758

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.Leu337Val
Coding: c.1009C>G
MANE Select: NM_001782
dbSNP: rs775851464
Type: single nucleotide variant
Location: chr9:35610695 (GRCh38)
Gene constraint: LOEUF 0.832 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.85
Residue 337: a disulfide bond; the c-type lectin domain

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-leu337val (accessed [today's date]).

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