Is CD44 p.Lys417Arg (c.1250A>G) pathogenic?

CD44 p.Lys417Arg (c.1250A>G) is classified Benign in CD44 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-16). AlphaMissense: likely benign (0.069); Common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with CD44-related disorder.

What condition is associated with CD44 p.Lys417Arg (c.1250A>G)?

CD44 p.Lys417Arg (c.1250A>G) is associated with CD44-related disorder (ClinVar).

What do computational predictors say about CD44 p.Lys417Arg (c.1250A>G)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

CD44 p.Lys417Arg

Q: How common is CD44 p.Lys417Arg (c.1250A>G) in the general population?

CD44 p.Lys417Arg (c.1250A>G) is common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1250A>G · rs9666607 · VCV3059515

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 94.1%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD44-related disorder

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1	GERP -4.5, phastCons 0.08
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.099 · regional, not allelic
Overall
CADD	4.054	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 94.1% East Asian · 42,193/44,846 alleles

Filtering AF 93.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 93%

Overall 71% 1,144,256/1,611,714 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	94.1%	1
African / African-American	88.1%	1
South Asian	82.1%	1
Ashkenazi Jewishnot grpmax-eligible	76.8%	1
Finnishnot grpmax-eligible	73.2%	1
Remaining individualsnot grpmax-eligible	72.1%	1
Middle Eastern	71.3%	1
Admixed American	68.9%	1
European (non-Finnish)	68%	1
Amishnot grpmax-eligible	65.5%	2

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.Lys417Arg
Coding: c.1250A>G
MANE Select: NM_000610
dbSNP: rs9666607
Type: single nucleotide variant
Location: chr11:35204608 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 417: a UniProt-annotated variant site (in); 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.Glu374= Benign same condition
CD44 p.Ile479Thr 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-lys417arg (accessed [today's date]).

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