Is CD247 p.Ser56Ile (c.167G>T) pathogenic?

CD247 p.Ser56Ile (c.167G>T) is classified Uncertain significance in CD247 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-07). AlphaMissense: likely benign (0.1848); Ultra-rare (popmax 0.0317%, amr); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Ser56Ile (c.167G>T)?

CD247 p.Ser56Ile (c.167G>T) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Ser56Ile (c.167G>T) in the general population?

CD247 p.Ser56Ile (c.167G>T) is ultra-rare (popmax 0.0317%, amr) (gnomAD).

What do computational predictors say about CD247 p.Ser56Ile (c.167G>T)?

AlphaMissense predicts likely benign (score 0.1848) — an in-silico prediction, not a clinical call.

CD247 p.Ser56Ile

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.167G>T · rs372651048 · VCV1394874

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1848 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0317%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 25

Computational evidence

Protein change
AlphaMissense	0.1848	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -8.83	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.40	acceptor loss, 1 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.1	GERP 1.6, phastCons 0.99
Regional constraint	o/e 0.91	unconstrained · MANE · 87 kb · p 0.18 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0317% Admixed American · 19/60,006 alleles

Filtering AF 0.0207% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00167% 27/1,613,964 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0317%	3,158
African / African-American	0.00133%	74,936
South Asian	0.0011%	91,092
European (non-Finnish)	0.000509%	196,653

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.Ser56Ile
Coding: c.167G>T
MANE Select: NM_198053
dbSNP: rs372651048
Type: single nucleotide variant
Location: chr1:167439396 (GRCh38)
Gene constraint: LOEUF 0.633 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 62.36 · 38 PDB

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-ser56ile (accessed [today's date]).

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