Is CD72 p.His178Tyr (c.532C>T) pathogenic?

CD72 p.His178Tyr (c.532C>T) is classified Uncertain significance in CD72 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.1011); Ultra-rare (popmax 0.0133%, amr).

How common is CD72 p.His178Tyr (c.532C>T) in the general population?

CD72 p.His178Tyr (c.532C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about CD72 p.His178Tyr (c.532C>T)?

AlphaMissense predicts likely benign (score 0.1011) — an in-silico prediction, not a clinical call.

CD72 p.His178Tyr

c.532C>T · rs1033353378 · VCV2569643

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1011 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1011	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -10.45	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.1
Regional constraint	o/e 0.96	unconstrained · MANE · 7,676 bp · p 0.39 · regional, not allelic
Overall
CADD	0.824	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 0.0133% Admixed American · 8/59,998 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00483%

Overall 0.00124% 20/1,614,016 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.016%	6,249
Admixed Americangrpmax	0.0133%	7,500
European (non-Finnish)	0.000169%	590,023

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.His178Tyr
Coding: c.532C>T
MANE Select: NM_001782
dbSNP: rs1033353378
Type: single nucleotide variant
Location: chr9:35616099 (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-his178tyr (accessed [today's date]).

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