Is CD4 p.Leu344= (c.1030C>T) pathogenic?

CD4 p.Leu344= (c.1030C>T) is classified Likely benign in CD4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-02-22). Ultra-rare (popmax 0.0423%, eas); Associated with CD4-related disorder.

What condition is associated with CD4 p.Leu344= (c.1030C>T)?

CD4 p.Leu344= (c.1030C>T) is associated with CD4-related disorder (ClinVar).

How common is CD4 p.Leu344= (c.1030C>T) in the general population?

CD4 p.Leu344= (c.1030C>T) is ultra-rare (popmax 0.0423%, eas) (gnomAD).

CD4 p.Leu344=

c.1030C>T · rs201962054 · VCV3046774

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0423%, eas)

Conditions

CD4-related disorder

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 -0.13	GERP -1.6
Overall
CADD	0.988	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0423% East Asian · 19/44,892 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.023%

Overall 0.00143% 23/1,614,016 alleles · ultra-rare exomes 19/1,461,728 · genomes 4/152,288 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0423%	2,363
Remaining individualsnot grpmax-eligible	0.0064%	15,625

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.Leu344=
Coding: c.1030C>T
MANE Select: NM_000616
dbSNP: rs201962054
Type: single nucleotide variant
Location: chr12:6817204 (GRCh38)
Gene constraint: LOEUF 0.673 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.35 · 84 PDB
Residue 344: the ig-like c2-type 3 domain

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

Disease context

CD4-related disorder

Similar variants

CD4 p.Val360= Likely benign same condition
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

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-leu344 (accessed [today's date]).

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