Is CD44 p.Ile479Thr (c.1436T>C) pathogenic?

CD44 p.Ile479Thr (c.1436T>C) is classified Benign in CD44 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-16). AlphaMissense: likely benign (0.0534); Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with CD44-related disorder.

What condition is associated with CD44 p.Ile479Thr (c.1436T>C)?

CD44 p.Ile479Thr (c.1436T>C) is associated with CD44-related disorder (ClinVar).

What do computational predictors say about CD44 p.Ile479Thr (c.1436T>C)?

AlphaMissense predicts likely benign (score 0.0534) — an in-silico prediction, not a clinical call.

CD44 p.Ile479Thr

Q: How common is CD44 p.Ile479Thr (c.1436T>C) in the general population?

CD44 p.Ile479Thr (c.1436T>C) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1436T>C · rs1467558 · VCV3058927

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0534 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, 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	0.0534	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -3.62	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.41	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.9	GERP 1.9, phastCons 0.95
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.099 · regional, not allelic
Overall
CADD	17.31	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 100% East Asian · 44,818/44,834 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 83.6% 1,342,940/1,606,644 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
African / African-American	96.8%	1
South Asian	95%	1
Middle Eastern	93.6%	1
Ashkenazi Jewishnot grpmax-eligible	91.6%	1
Admixed American	91.6%	1
Remaining individualsnot grpmax-eligible	85.1%	1
Finnishnot grpmax-eligible	84.3%	1
European (non-Finnish)	80.5%	1
Amishnot grpmax-eligible	79.4%	1

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.Ile479Thr
Coding: c.1436T>C
MANE Select: NM_000610
dbSNP: rs1467558
Type: single nucleotide variant
Location: chr11:35208126 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 479: the 'stem' region; a UniProt-annotated variant site (in); 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.Lys417Arg 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-ile479thr (accessed [today's date]).

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