Is CD44 p.Glu374= (c.1122G>A) pathogenic?

CD44 p.Glu374= (c.1122G>A) is classified Benign in CD44 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-01-28). Common (popmax 29.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CD44-related disorder.

What condition is associated with CD44 p.Glu374= (c.1122G>A)?

CD44 p.Glu374= (c.1122G>A) is associated with CD44-related disorder (ClinVar).

CD44 p.Glu374=

Q: How common is CD44 p.Glu374= (c.1122G>A) in the general population?

CD44 p.Glu374= (c.1122G>A) is common (popmax 29.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1122G>A · rs11033026 · VCV3056005

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 29.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CD44-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.02	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -9.4	GERP -4.8
Overall
CADD	0.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 29.3% African / African-American · 21,941/74,846 alleles

Filtering AF 29% ClinGen BA1/BS1 input FAF95, joint · FAF99 28.9%

Overall 1.59% 25,626/1,613,606 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	29.3%	3
Remaining individualsnot grpmax-eligible	2.06%	49
Admixed American	2.04%	49
Middle Eastern	1.5%	67
Ashkenazi Jewishnot grpmax-eligible	0.128%	779
European (non-Finnish)	0.0822%	1,216
South Asian	0.0703%	1,423
Finnishnot grpmax-eligible	0.0109%	9,147
East Asian	0.00446%	22,433

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.Glu374=
Coding: c.1122G>A
MANE Select: NM_000610
dbSNP: rs11033026
Type: single nucleotide variant
Location: chr11:35201756 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 374: the 'stem' region; the 'disordered' region

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.Ile479Thr Benign same condition
CD44 p.Lys417Arg Benign same condition
CD44 p.Thr216= Likely 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-glu374 (accessed [today's date]).

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