Is CD44 p.Glu37Ala (c.110A>C) pathogenic?

CD44 p.Glu37Ala (c.110A>C) is classified Uncertain significance in CD44 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-24). AlphaMissense: likely pathogenic (0.9724); Absent from gnomAD v4.1.

How common is CD44 p.Glu37Ala (c.110A>C) in the general population?

CD44 p.Glu37Ala (c.110A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD44 p.Glu37Ala (c.110A>C)?

AlphaMissense predicts likely pathogenic (score 0.9724) — an in-silico prediction, not a clinical call.

CD44 p.Glu37Ala

c.110A>C · rs2495815931 · VCV2478814

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9724 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9724	likely pathogenic · top 5% in CD44
REVEL	0.432	indeterminate
SaProt	LLR -9.73	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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 0.78	unconstrained · MANE · 58 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD44
Protein: p.Glu37Ala
Coding: c.110A>C
MANE Select: NM_000610
dbSNP: rs2495815931
Type: single nucleotide variant
Location: chr11:35176617 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 37: a disulfide bond; the link domain; a β-strand

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

Similar variants

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
CD44 p.Thr393Met 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-glu37ala (accessed [today's date]).

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