Is CD4 p.Ser341= (c.1023T>C) pathogenic?

CD4 p.Ser341= (c.1023T>C) is classified Benign in CD4 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-24). Common (popmax 90.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 79.

What condition is associated with CD4 p.Ser341= (c.1023T>C)?

CD4 p.Ser341= (c.1023T>C) is associated with immunodeficiency 79 (ClinVar).

CD4 p.Ser341=

Q: How common is CD4 p.Ser341= (c.1023T>C) in the general population?

CD4 p.Ser341= (c.1023T>C) is common (popmax 90.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1023T>C · rs1055141 · VCV1192706

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 90.8%, 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 -0.072	GERP -4.1, phastCons 0.011
Overall
CADD	7.075	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 90.8% East Asian · 40,727/44,878 alleles

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

Overall 58.6% 946,325/1,613,520 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	90.8%	1
African / African-American	75.4%	1
South Asian	70.6%	1
Admixed American	66.7%	1
Finnishnot grpmax-eligible	66.1%	2
Middle Eastern	61.3%	2
Remaining individualsnot grpmax-eligible	60.2%	2
Ashkenazi Jewishnot grpmax-eligible	57.6%	2
European (non-Finnish)	54.6%	2
Amishnot grpmax-eligible	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.Ser341=
Coding: c.1023T>C
MANE Select: NM_000616
dbSNP: rs1055141
Type: single nucleotide variant
Location: chr12:6817197 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 341: a disulfide bond; the ig-like c2-type 3 domain

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.Cys447= 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-ser341 (accessed [today's date]).

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