Is CD44 p.Thr480Met (c.1439C>T) pathogenic?

CD44 p.Thr480Met (c.1439C>T) is classified Uncertain significance in CD44 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). AlphaMissense: likely benign (0.0889); Very rare (popmax 0.00892%, eas).

How common is CD44 p.Thr480Met (c.1439C>T) in the general population?

CD44 p.Thr480Met (c.1439C>T) is very rare (popmax 0.00892%, eas) (gnomAD).

What do computational predictors say about CD44 p.Thr480Met (c.1439C>T)?

AlphaMissense predicts likely benign (score 0.0889) — an in-silico prediction, not a clinical call.

CD44 p.Thr480Met

c.1439C>T · VCV3488094

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0889 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00892%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0889	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -9.72	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.19	GERP -3.9, phastCons 0.003
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.099 · regional, not allelic
Overall
CADD	13.98	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00892% East Asian · 4/44,850 alleles

Filtering AF 0.0036% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00322%

Overall 0.00466% 75/1,609,868 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00962%	10,390
East Asiangrpmax	0.00892%	11,212
Admixed American	0.00667%	14,992
European (non-Finnish)	0.00459%	21,784
South Asian	0.0044%	22,749
African / African-American	0.00401%	24,937

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr480Met
Coding: c.1439C>T
MANE Select: NM_000610
Type: single nucleotide variant
Location: chr11:35208129 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 480: the 'stem' region; the 'disordered' region

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-thr480met (accessed [today's date]).

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