Is CD247 p.Asp84His (c.250G>C) pathogenic?

CD247 p.Asp84His (c.250G>C) is classified Uncertain significance in CD247 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-15). AlphaMissense: ambiguous (0.4557); Very rare (popmax 0.00136%, nfe); Associated with immunodeficiency 25.

What condition is associated with CD247 p.Asp84His (c.250G>C)?

CD247 p.Asp84His (c.250G>C) is associated with immunodeficiency 25 (ClinVar).

How common is CD247 p.Asp84His (c.250G>C) in the general population?

CD247 p.Asp84His (c.250G>C) is very rare (popmax 0.00136%, nfe) (gnomAD).

What do computational predictors say about CD247 p.Asp84His (c.250G>C)?

AlphaMissense predicts ambiguous (score 0.4557) — an in-silico prediction, not a clinical call.

CD247 p.Asp84His

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>C · rs753572867 · VCV581037

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4557 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00136%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

immunodeficiency 25

Computational evidence

Protein change
AlphaMissense	0.4557	ambiguous
REVEL	0.181	moderately benign-leaning
SaProt	LLR -7.65	tolerated
⇒ REVEL and SaProt both call this tolerated; 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	24.1	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 0.00136% European (non-Finnish) · 16/1,179,926 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00105% 17/1,613,956 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)grpmax	0.00136%	73,745

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp84His
Coding: c.250G>C
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.Asp84Tyr 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-asp84his (accessed [today's date]).

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