Is CD44 p.Arg46Gln (c.137G>A) pathogenic?

CD44 p.Arg46Gln (c.137G>A) is classified Benign in CD44 (ClinVar, No assertion criteria, 1 submitter; last evaluated 1994-01-15). AlphaMissense: likely benign (0.1834); Very rare (popmax 0.00223%, eas); Associated with INDIAN BLOOD GROUP SYSTEM POLYMORPHISM.

What condition is associated with CD44 p.Arg46Gln (c.137G>A)?

CD44 p.Arg46Gln (c.137G>A) is associated with INDIAN BLOOD GROUP SYSTEM POLYMORPHISM (ClinVar).

How common is CD44 p.Arg46Gln (c.137G>A) in the general population?

CD44 p.Arg46Gln (c.137G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CD44 p.Arg46Gln (c.137G>A)?

AlphaMissense predicts likely benign (score 0.1834) — an in-silico prediction, not a clinical call.

CD44 p.Arg46Gln

c.137G>A · rs369473842 · VCV599021

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1834 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

INDIAN BLOOD GROUP SYSTEM POLYMORPHISM

Computational evidence

Protein change
AlphaMissense	0.1834	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -7.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -3, phastCons 0.81
Regional constraint	o/e 0.78	unconstrained · MANE · 58 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	21.4	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 0.00223% East Asian · 1/44,884 alleles

Overall 0.000137% 2/1,461,840 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,884
European (non-Finnish)	8.47e-05%	1,179,999

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: CD44
Protein: p.Arg46Gln
Coding: c.137G>A
MANE Select: NM_000610
dbSNP: rs369473842
Type: single nucleotide variant
Location: chr11:35176644 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 46: a disulfide bond; the link domain; a UniProt-annotated variant site (in in(a) antigen); an α-helix

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

Disease context

INDIAN BLOOD GROUP SYSTEM POLYMORPHISM

Similar variants

CD44 p.Arg46Trp Uncertain significance ★ ⚠ same residue
CD44 c.1282+10G>A Likely benign same condition
CD44 c.*1C>G Likely 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 p.Thr216= Likely benign 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/cd44-p-arg46gln (accessed [today's date]).

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