Is CD247 p.Ala59= (c.177A>G) pathogenic?

CD247 p.Ala59= (c.177A>G) is classified Benign/Likely benign in CD247 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-21). Rare (popmax 0.902%, sas); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Ala59= (c.177A>G)?

CD247 p.Ala59= (c.177A>G) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Ala59= (c.177A>G) in the general population?

CD247 p.Ala59= (c.177A>G) is rare (popmax 0.902%, sas) (gnomAD).

CD247 p.Ala59=

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.177A>G · rs373031213 · VCV466352

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.902%, sas)

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 -5.5	GERP -3.2
Overall
CADD	8.876	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.902% South Asian · 822/91,090 alleles

Filtering AF 0.851% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.831%

Overall 0.0572% 924/1,614,150 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.902%	111
Remaining individualsnot grpmax-eligible	0.0592%	1,689
Middle Eastern	0.033%	3,031
European (non-Finnish)	0.005%	20,000
Admixed American	0.00333%	30,013
African / African-American	0.00266%	37,525

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.Ala59=
Coding: c.177A>G
MANE Select: NM_198053
dbSNP: rs373031213
Type: single nucleotide variant
Location: chr1:167439386 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 59: a β-strand

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.Ala59Thr Uncertain significance ★ ⚠ same residue
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

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-ala59 (accessed [today's date]).

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