Is CD247 p.Ala120= (c.360G>A) pathogenic?

CD247 p.Ala120= (c.360G>A) is classified Likely benign in CD247 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-22). Rare (popmax 0.325%, amr); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Ala120= (c.360G>A)?

CD247 p.Ala120= (c.360G>A) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Ala120= (c.360G>A) in the general population?

CD247 p.Ala120= (c.360G>A) is rare (popmax 0.325%, amr) (gnomAD).

CD247 p.Ala120=

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.360G>A · rs568106106 · VCV704386

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.325%, amr)

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 -20	GERP -5.2
Overall
CADD	0.478	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.325% Admixed American · 195/60,026 alleles

Filtering AF 0.288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.273%

Overall 0.0132% 213/1,614,110 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.325%	308
Middle Eastern	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401
East Asian	0.00668%	14,961
South Asian	0.00439%	22,771
African / African-American	0.004%	25,016
European (non-Finnish)	0.000254%	393,317

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.Ala120=
Coding: c.360G>A
MANE Select: NM_198053
dbSNP: rs568106106
Type: single nucleotide variant
Location: chr1:167434053 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 120: the itam 2 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.Ala120Val Uncertain significance ★★ ⚠ same residue
CD247 p.Gln101Ter Pathogenic/Likely pathogenic ★★ same condition
CD247 c.58+6G>T 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-ala120 (accessed [today's date]).

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