CD4 p.Ser456=
c.1368C>T · rs28919579 · VCV718668
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.51%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.19 | GERP -3.3 |
| Overall | ||
| CADD | 3.937 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.51%
South Asian · 2,286/91,078 alleles
Filtering AF
2.42%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.39%
Overall
0.246%
3,977/1,614,090 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.51% | 40 |
| East Asian | 2.22% | 45 |
| Remaining individualsnot grpmax-eligible | 0.331% | 302 |
| Middle Eastern | 0.198% | 505 |
| Ashkenazi Jewishnot grpmax-eligible | 0.176% | 569 |
| Finnishnot grpmax-eligible | 0.0797% | 1,255 |
| European (non-Finnish) | 0.0294% | 3,400 |
| African / African-American | 0.0213% | 4,690 |
| Admixed American | 0.015% | 6,670 |
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
- CD4
- Protein
- p.Ser456=
- Coding
- c.1368C>T
- MANE Select
- NM_000616
- dbSNP
- rs28919579
- Type
- single nucleotide variant
- Location
- chr12:6819320 (GRCh38)
- Gene constraint
- LOEUF 0.673 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 84 PDB
- Residue 456
- a modified residue (phosphoserine)
Similar variants
- CD4 p.Ser352Trp Uncertain significance ★★ ⚠ same type
- CD4 p.Thr444Ala Uncertain significance ★★ ⚠ same type
- CD4 c.1346+55T>G Benign ★★ same type
- CD4 c.49+35A>G Benign ★★ same type
- CD4 c.*91C>A Benign ★★ same type
- CD4 c.*92A>G Benign ★★ same type
- CD4 p.Arg265Trp Benign ★★ ⚠ same type
- CD4 p.Arg431Gln Benign/Likely benign ★★ ⚠ 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/cd4-p-ser456 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown