CD4 c.49+35A>G
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele
Conditions
1
immunodeficiency 79
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +35 | near-intronic (+35 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.57 | GERP -3.2, phastCons 0.03 |
| Non-coding constraint | Z 2.24 | 1 kb window · o/e 0.83 · regional · uncalibrated |
| Overall | ||
| CADD | 9.028 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
100%
East Asian · 44,825/44,838 alleles
Filtering AF
99.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 98.9%
Overall
92.8%
1,496,681/1,612,746 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 100% | 1 |
| African / African-American | 98.7% | 1 |
| South Asian | 97.6% | 1 |
| Middle Eastern | 96% | 1 |
| Finnishnot grpmax-eligible | 94.9% | 1 |
| Amishnot grpmax-eligible | 94.8% | 1 |
| Remaining individualsnot grpmax-eligible | 93.4% | 1 |
| Ashkenazi Jewishnot grpmax-eligible | 93.3% | 1 |
| European (non-Finnish) | 92.4% | 1 |
| Admixed American | 78.2% | 1 |
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
- Coding
- c.49+35A>G
- MANE Select
- NM_000616
- dbSNP
- rs2365568
- Type
- single nucleotide variant
- Location
- chr12:6800222 (GRCh38)
- Gene constraint
- LOEUF 0.673 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.35 · 84 PDB
Similar variants
- CD4 p.Thr444Ala Uncertain significance ★★ ⚠ same condition
- CD4 c.1346+55T>G Benign ★★ same condition
- CD4 c.*91C>A Benign ★★ same condition
- CD4 c.*92A>G Benign ★★ same condition
- CD4 p.Cys447= Benign ★★ same condition
- CD4 p.Ser341= Benign ★★ same condition
- CD4 p.Thr267Ala Uncertain significance ★ ⚠ same condition
- CD4 c.1157-1G>A Pathogenic same condition
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-c-49-plus-35a-g (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown