Is CD247 p.Tyr83= (c.249C>T) pathogenic?

CD247 p.Tyr83= (c.249C>T) is classified Benign/Likely benign in CD247 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Common (popmax 15.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 25.

What condition is associated with CD247 p.Tyr83= (c.249C>T)?

CD247 p.Tyr83= (c.249C>T) is associated with immunodeficiency 25 (ClinVar).

CD247 p.Tyr83=

Q: How common is CD247 p.Tyr83= (c.249C>T) in the general population?

CD247 p.Tyr83= (c.249C>T) is common (popmax 15.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.249C>T · rs33937946 · VCV466354

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Common

common (popmax 15.8%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

immunodeficiency 25

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 -2.1	GERP -4.9
Overall
CADD	0.492	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15.8% African / African-American · 11,812/74,884 alleles

Filtering AF 15.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.4%

Overall 4.27% 68,810/1,613,172 alleles · common exomes 58,436/1,461,024 · genomes 10,374/152,148 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15.8%	6
Middle Eastern	4.79%	21
Ashkenazi Jewishnot grpmax-eligible	4.56%	22
Remaining individualsnot grpmax-eligible	4.34%	23
European (non-Finnish)	4.11%	24
Admixed American	3.23%	31
Finnishnot grpmax-eligible	2.28%	44
South Asian	0.881%	114
Amishnot grpmax-eligible	0.329%	304
East Asian	0.00669%	14,957

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.Tyr83=
Coding: c.249C>T
MANE Select: NM_198053
dbSNP: rs33937946
Type: single nucleotide variant
Location: chr1:167438621 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 83: a modified residue (phosphotyrosine); a β-strand; the itam 1 domain; the 'disordered' region

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-tyr83 (accessed [today's date]).

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