CD74 p.Pro280=
c.840G>A · VCV3998331
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0387%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.036 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -4.9 | GERP -2.6 |
| Overall | ||
| CADD | 3.926 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0387%
African / African-American · 29/74,996 alleles
Filtering AF
0.0276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0238%
Overall
0.0158%
254/1,612,602 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0387% | 2,586 |
| European (non-Finnish) | 0.0178% | 5,615 |
| Remaining individualsnot grpmax-eligible | 0.0144% | 6,935 |
| South Asian | 0.0044% | 22,731 |
| Admixed American | 0.00168% | 59,678 |
| Finnishnot grpmax-eligible | 0.00156% | 64,020 |
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
- CD74
- Protein
- p.Pro280=
- Coding
- c.840G>A
- MANE Select
- NM_001025159
- Type
- single nucleotide variant
- Location
- chr5:150402603 (GRCh38)
- Gene constraint
- LOEUF 0.849 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.49 · 24 PDB
- Residue 280
- the 'disordered' region
Similar variants
- CD74 p.Pro280Gln Uncertain significance ★ ⚠ same residue
- CD74 p.Ala117Thr Uncertain significance ★ ⚠ same type
- CD74 p.Arg108Gly Uncertain significance ★ ⚠ same type
- CD74 p.Arg108His Uncertain significance ★ ⚠ same type
- CD74 p.Arg167Ser Uncertain significance ★ ⚠ same type
- CD74 p.Arg35Gly Uncertain significance ★ ⚠ same type
- CD74 p.Arg46His Uncertain significance ★ ⚠ same type
- CD74 p.Arg77Trp 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/cd74-p-pro280 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown