Is CD44 p.Lys739Gln (c.2215A>C) pathogenic?

CD44 p.Lys739Gln (c.2215A>C) is classified Uncertain significance in CD44 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-27). AlphaMissense: likely pathogenic (0.7574); Ultra-rare (popmax 0.0588%, afr).

How common is CD44 p.Lys739Gln (c.2215A>C) in the general population?

CD44 p.Lys739Gln (c.2215A>C) is ultra-rare (popmax 0.0588%, afr) (gnomAD).

What do computational predictors say about CD44 p.Lys739Gln (c.2215A>C)?

AlphaMissense predicts likely pathogenic (score 0.7574) — an in-silico prediction, not a clinical call.

CD44 p.Lys739Gln

c.2215A>C · rs200314711 · VCV2211734

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7574 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0588%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7574	likely pathogenic
REVEL	0.257	benign-leaning
SaProt	LLR -6.77	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.6, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.099 · regional, not allelic
Overall
CADD	25.2	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 0.0588% African / African-American · 44/74,844 alleles

Filtering AF 0.0449% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0401%

Overall 0.00354% 57/1,611,084 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0588%	1,701
Remaining individualsnot grpmax-eligible	0.0112%	8,909
Admixed American	0.00834%	11,996
South Asian	0.0011%	91,018

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.Lys739Gln
Coding: c.2215A>C
MANE Select: NM_000610
dbSNP: rs200314711
Type: single nucleotide variant
Location: chr11:35229319 (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

Similar variants

CD44 p.Lys739Thr Uncertain significance ★ ⚠ same residue
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

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-lys739gln (accessed [today's date]).

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