Is CD44 p.Ala20Thr (c.58G>A) pathogenic?

CD44 p.Ala20Thr (c.58G>A) is classified Uncertain significance in CD44 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: ambiguous (0.4361); Very rare (popmax 0.000284%).

How common is CD44 p.Ala20Thr (c.58G>A) in the general population?

CD44 p.Ala20Thr (c.58G>A) is very rare (popmax 0.000284%) (gnomAD).

What do computational predictors say about CD44 p.Ala20Thr (c.58G>A)?

AlphaMissense predicts ambiguous (score 0.4361) — an in-silico prediction, not a clinical call.

CD44 p.Ala20Thr

c.58G>A · rs1383216966 · VCV2615985

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4361 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000284%)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4361	ambiguous
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.18	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.37, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 58 kb · p 7.9e-05 · regional, not allelic
Overall
CADD	24.8	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 0.000284%

Overall 0.000284% 4/1,406,842 alleles · very rare

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.Ala20Thr
Coding: c.58G>A
MANE Select: NM_000610
dbSNP: rs1383216966
Type: single nucleotide variant
Location: chr11:35139361 (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 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-ala20thr (accessed [today's date]).

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