Is CD44 p.Thr216= (c.648A>C) pathogenic?

CD44 p.Thr216= (c.648A>C) is classified Likely benign in CD44 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-01). Ultra-rare (popmax 0.0136%, nfe); Associated with CD44-related disorder.

What condition is associated with CD44 p.Thr216= (c.648A>C)?

CD44 p.Thr216= (c.648A>C) is associated with CD44-related disorder (ClinVar).

How common is CD44 p.Thr216= (c.648A>C) in the general population?

CD44 p.Thr216= (c.648A>C) is ultra-rare (popmax 0.0136%, nfe) (gnomAD).

CD44 p.Thr216=

c.648A>C · rs769999943 · VCV3043576

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Conditions

CD44-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.002	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -3.8
Overall
CADD	0.742	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% European (non-Finnish) · 161/1,179,772 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0113%

Overall 0.0102% 164/1,613,818 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,328
Remaining individualsnot grpmax-eligible	0.0048%	20,827

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: CD44
Protein: p.Thr216=
Coding: c.648A>C
MANE Select: NM_000610
dbSNP: rs769999943
Type: single nucleotide variant
Location: chr11:35190046 (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

CD44-related disorder

Similar variants

CD44 c.1282+10G>A Likely benign same condition
CD44 c.*1C>G Likely benign same condition
CD44 p.Arg46Gln Benign ⚠ same condition
CD44 p.Asp243= Likely benign same condition
CD44 p.Glu374= Benign same condition
CD44 p.Ile479Thr Benign same condition
CD44 p.Lys417Arg Benign same condition
CD44 c.367+7T>C 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-p-thr216 (accessed [today's date]).

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