Is CD44 p.Ile457Val (c.1369A>G) pathogenic?

CD44 p.Ile457Val (c.1369A>G) is classified Benign in CD44 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-18). AlphaMissense: likely benign (0.0731); Low-frequency (popmax 2.58%, sas).

How common is CD44 p.Ile457Val (c.1369A>G) in the general population?

CD44 p.Ile457Val (c.1369A>G) is low-frequency (popmax 2.58%, sas) (gnomAD).

What do computational predictors say about CD44 p.Ile457Val (c.1369A>G)?

AlphaMissense predicts likely benign (score 0.0731) — an in-silico prediction, not a clinical call.

CD44 p.Ile457Val

c.1369A>G · rs140510483 · VCV708949

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0731 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.58%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0731	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -5.77	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 0.078	GERP -5, phastCons 0.001
Regional constraint	o/e 1.07	unconstrained · MANE · 32 kb · p 0.099 · regional, not allelic
Overall
CADD	0.545	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 2.58% South Asian · 2,345/90,790 alleles

Filtering AF 2.5% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.46%

Overall 0.258% 4,164/1,612,208 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	2.58%	39
Middle Eastern	1.78%	56
Remaining individualsnot grpmax-eligible	0.356%	281
Ashkenazi Jewishnot grpmax-eligible	0.318%	314
Admixed American	0.149%	672
European (non-Finnish)	0.109%	918
African / African-American	0.0227%	4,404
East Asian	0.00447%	22,362
Finnishnot grpmax-eligible	0.00313%	31,994

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.Ile457Val
Coding: c.1369A>G
MANE Select: NM_000610
dbSNP: rs140510483
Type: single nucleotide variant
Location: chr11:35206198 (GRCh38)
Gene constraint: LOEUF 0.654 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.31 · 7 PDB
Residue 457: 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.Phe245= Benign ★★ same type
CD44 p.Thr163= Benign ★★ same type
CD44 p.Thr393Met Benign ★★ same type
CD44 p.Thr415= 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-ile457val (accessed [today's date]).

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