Is CD4 p.Cys447= (c.1341T>C) pathogenic?

CD4 p.Cys447= (c.1341T>C) is classified Benign in CD4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-24). Common (popmax 90.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 79.

What condition is associated with CD4 p.Cys447= (c.1341T>C)?

CD4 p.Cys447= (c.1341T>C) is associated with immunodeficiency 79 (ClinVar).

CD4 p.Cys447=

Q: How common is CD4 p.Cys447= (c.1341T>C) in the general population?

CD4 p.Cys447= (c.1341T>C) is common (popmax 90.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1341T>C · rs12821756 · VCV1192707

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 90.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency 79

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 -1	GERP -3.5
Overall
CADD	3.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.7% East Asian · 40,391/44,512 alleles

Filtering AF 90% ClinGen BA1/BS1 input FAF95, joint · FAF99 89.7%

Overall 58.9% 936,431/1,590,994 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	90.7%	1
African / African-American	78.5%	1
South Asian	70.8%	1
Admixed American	67.1%	1
Finnishnot grpmax-eligible	66.6%	2
Middle Eastern	61.3%	2
Remaining individualsnot grpmax-eligible	60.6%	2
Ashkenazi Jewishnot grpmax-eligible	58.5%	2
Amishnot grpmax-eligible	54.7%	2
European (non-Finnish)	54.5%	2

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.Cys447=
Coding: c.1341T>C
MANE Select: NM_000616
dbSNP: rs12821756
Type: single nucleotide variant
Location: chr12:6818909 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 447: the 'hiv-1 vpu-susceptibility domain' region

Full CD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 79 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CD4 p.Thr444Ala Uncertain significance ★★ ⚠ same condition
CD4 c.1346+55T>G Benign ★★ same condition
CD4 c.49+35A>G Benign ★★ same condition
CD4 c.*91C>A Benign ★★ same condition
CD4 c.*92A>G 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-p-cys447 (accessed [today's date]).

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