Is CD44 c.436+3A>G pathogenic?

CD44 c.436+3A>G is classified Uncertain significance in CD44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-10). Absent from gnomAD v4.1; Associated with immunodeficiency due to CD25 deficiency.

What condition is associated with CD44 c.436+3A>G?

CD44 c.436+3A>G is associated with immunodeficiency due to CD25 deficiency (ClinVar).

How common is CD44 c.436+3A>G in the general population?

CD44 c.436+3A>G is absent from gnomAD v4.1 (gnomAD).

How is Immunodeficiency due to CD25 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

CD44 c.436+3A>G

VCV4278029

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

immunodeficiency due to CD25 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +3	donor splice region (+3, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	Δ0.24	donor loss · deltas
Pangolin	Δ0.49	loss · gain 0.02 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6.9	GERP 2.5, phastCons 1
Non-coding constraint	Z 1.14	1 kb window · o/e 0.91 · regional · uncalibrated
Overall
CADD	18.42	PHRED · no single calibrated threshold — expert panels disagree

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: CD44
Coding: c.436+3A>G
MANE Select: NM_000610
Type: single nucleotide variant
Location: chr11:35186903 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB

Full CD44 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency due to CD25 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Immunodeficiency due to CD25 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

CD44 c.367+7T>C Benign ★★ same type
CD44 p.Arg463Gln Benign ★★ same type
CD44 p.Arg673Gln Likely benign ★★ ⚠ same type
CD44 p.Gly462= Benign ★★ same type
CD44 p.Ile457Val Benign ★★ same type
CD44 p.Phe245= Benign ★★ same type
CD44 p.Thr163= Benign ★★ same type
CD44 p.Thr393Met Benign ★★ ⚠ same type

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/cd44-c-436-plus-3a-g (accessed [today's date]).

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