Is CD247 p.Glu82= (c.246G>A) pathogenic?

CD247 p.Glu82= (c.246G>A) is classified Benign in CD247 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-02). Common (popmax 6.48%, afr) — too common for a highly-penetrant pathogenic allele; Associated with immunodeficiency 25.

What condition is associated with CD247 p.Glu82= (c.246G>A)?

CD247 p.Glu82= (c.246G>A) is associated with immunodeficiency 25 (ClinVar).

CD247 p.Glu82=

Q: How common is CD247 p.Glu82= (c.246G>A) in the general population?

CD247 p.Glu82= (c.246G>A) is common (popmax 6.48%, 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.246G>A · rs34940956 · VCV466353

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Common

common (popmax 6.48%, 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 -1	GERP -4.9, phastCons 0.002
Overall
CADD	5.865	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.48% African / African-American · 4,861/75,016 alleles

Filtering AF 6.33% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.27%

Overall 0.346% 5,578/1,614,060 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.48%	15
Remaining individualsnot grpmax-eligible	0.47%	213
Admixed American	0.446%	224
Middle Eastern	0.429%	233
South Asian	0.0285%	3,503
European (non-Finnish)	0.00873%	11,455

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.Glu82=
Coding: c.246G>A
MANE Select: NM_198053
dbSNP: rs34940956
Type: single nucleotide variant
Location: chr1:167438624 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 82: an α-helix; the itam 1 domain

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-glu82 (accessed [today's date]).

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