Is CD247 p.Asp84Tyr (c.250G>T) pathogenic?

CD247 p.Asp84Tyr (c.250G>T) is classified Uncertain significance in CD247 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-04). AlphaMissense: ambiguous (0.4532); Absent from gnomAD v4.1; Associated with immunodeficiency 25.

What condition is associated with CD247 p.Asp84Tyr (c.250G>T)?

CD247 p.Asp84Tyr (c.250G>T) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Asp84Tyr (c.250G>T) in the general population?

CD247 p.Asp84Tyr (c.250G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD247 p.Asp84Tyr (c.250G>T)?

AlphaMissense predicts ambiguous (score 0.4532) — an in-silico prediction, not a clinical call.

CD247 p.Asp84Tyr

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.250G>T · rs753572867 · VCV1038153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

immunodeficiency 25

Computational evidence

Protein change
AlphaMissense	0.4532	ambiguous
REVEL	0.217	benign-leaning
SaProt	LLR -10.65	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 87 kb · p 0.18 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD247
Protein: p.Asp84Tyr
Coding: c.250G>T
MANE Select: NM_198053
dbSNP: rs753572867
Type: single nucleotide variant
Location: chr1:167438620 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 84: 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.Asp84Ala Uncertain significance ★ ⚠ same residue
CD247 p.Asp84Asn Uncertain significance ★ ⚠ same residue
CD247 p.Asp84His Uncertain significance ★ ⚠ same residue
CD247 p.Asp84Gly Likely benign ★ 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

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-asp84tyr (accessed [today's date]).

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