Is CD247 p.Leu34= (c.100C>T) pathogenic?

CD247 p.Leu34= (c.100C>T) is classified Benign/Likely benign in CD247 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-26). Rare (popmax 0.383%, eas); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Leu34= (c.100C>T)?

CD247 p.Leu34= (c.100C>T) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Leu34= (c.100C>T) in the general population?

CD247 p.Leu34= (c.100C>T) is rare (popmax 0.383%, eas) (gnomAD).

CD247 p.Leu34=

Q: How is T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.100C>T · rs181342622 · VCV723755

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.383%, eas)

Conditions

immunodeficiency 25

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.5	GERP -4.8, phastCons 1
Overall
CADD	8.217	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.383% East Asian · 172/44,886 alleles

Filtering AF 0.336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.318%

Overall 0.0153% 247/1,613,850 alleles · rare exomes 213/1,461,502 · genomes 34/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.383%	261
South Asian	0.0571%	1,751
Remaining individualsnot grpmax-eligible	0.032%	3,125
Middle Eastern	0.0165%	6,062
Admixed American	0.00167%	60,024
European (non-Finnish)	8.48e-05%	1,179,908

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: CD247
Protein: p.Leu34=
Coding: c.100C>T
MANE Select: NM_198053
dbSNP: rs181342622
Type: single nucleotide variant
Location: chr1:167440726 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 34: an α-helix

Full CD247 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 25 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For T-B+ severe combined immunodeficiency due to CD3delta/CD3epsilon/CD3zeta (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CD247 p.Gln101Ter Pathogenic/Likely pathogenic ★★ same condition
CD247 c.58+6G>T Uncertain significance ★★ same condition
CD247 p.Ala120Val Uncertain significance ★★ ⚠ same condition
CD247 p.Ala63Pro Uncertain significance ★★ ⚠ same condition
CD247 p.Ala9Thr Uncertain significance ★★ ⚠ same condition
CD247 p.Arg103Lys Uncertain significance ★★ ⚠ same condition
CD247 p.Arg132Cys Uncertain significance ★★ ⚠ same condition
CD247 p.Arg132His Uncertain significance ★★ ⚠ 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/cd247-p-leu34 (accessed [today's date]).

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