Is CD247 p.Phe50Leu (c.148T>C) pathogenic?

CD247 p.Phe50Leu (c.148T>C) is classified Uncertain significance in CD247 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.9186); Ultra-rare (popmax 0.0165%, mid); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Phe50Leu (c.148T>C)?

CD247 p.Phe50Leu (c.148T>C) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Phe50Leu (c.148T>C) in the general population?

CD247 p.Phe50Leu (c.148T>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about CD247 p.Phe50Leu (c.148T>C)?

AlphaMissense predicts likely pathogenic (score 0.9186) — an in-silico prediction, not a clinical call.

CD247 p.Phe50Leu

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.148T>C · rs147458563 · VCV1005445

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9186 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 25

Computational evidence

Protein change
AlphaMissense	0.9186	likely pathogenic · top 5% in CD247
REVEL	0.176	moderately benign-leaning
SaProt	LLR -9.97	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 87 kb · p 0.18 · regional, not allelic
Overall
CADD	26.0	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

Grpmax group 0.0165% Middle Eastern · 1/6,076 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00965%

Overall 0.00961% 155/1,612,152 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,076
African / African-American	0.012%	8,322
European (non-Finnish)	0.0119%	8,418
Remaining individualsnot grpmax-eligible	0.00481%	20,809
Admixed American	0.00333%	29,999

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.Phe50Leu
Coding: c.148T>C
MANE Select: NM_198053
dbSNP: rs147458563
Type: single nucleotide variant
Location: chr1:167440678 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB
Residue 50: an α-helix

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-phe50leu (accessed [today's date]).

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